Artemisia annua et Coronavirus

Publications relatives au potentiel antiviral et immunostimulant d’Artemisia annua L.

Cet article présente et permet l’accès aux recherches publiées relatives aux propriétés antivirales, immunomodulatrices et immunoprotectrices d’Artemisia annua et de ses principes actifs. Les études et leurs résumés sont présentés selon la chronologie de leur publication depuis la première publication en 2004, d’une étude l’OMS mentionnant l’utilisation d’Artemisia annua dans le cadre du traitement du SARS-CoV2.

Artemisia annua et Coronavirus

Publications relatives au potentiel antiviral et immunostimulant d’Artemisia annua L.

2004

World Health Organization
SARS Clinical trials on treatment using a combination of Traditional Chinese medicine and Western medicine. Report of the WHO International Expert Meeting to review and analyse clinical reports on combination treatment for SARS 8–10 October 2003 Beijing, People’s Republic of China
World Health Organization Geneva 2004

SARS Clinical trials on treatment using a combination of Traditional Chinese medicine and Western medicine

No abstract

Introduction excerpts :

In the winter of 2002, severe acute respiratory syndrome (SARS) began to spread throughout the world. [...] A total of 21 research projects were initiated to cover three aspects of SARS, namely, prevention, treatment and rehabilitation. [...] Of the 5327 patients with confirmed SARS, 3104 received treatment with TCM, which was 58.3% of the total SARS patients in China. [...] In order to better understand the potential of complementary treatment for patients with SARS and to encourage robust clinical research on SARS and its treatment with traditional medicine, the Chinese Government requested the guidance of WHO and support for 13 clinical trials of integrated treatment with TCM and Western medicine for SARS patients.

First level There were sufficient data in the clinical reports to show that integrated treatment with TCM and Western medicine for patients with SARS is safe. Second level Of the reported trials, only two clinical trials included patients who were randomly selected for the studies, the others were prospective cohort studies or retrospective studies. The experts considered that the data were insufficient although it was concluded that there could be potential clinical benefits from integrated treatment with TCM and Western medicine for patients with SARS. Such potential benefits include the alleviation of fatigue, shortness of breath and other clinical symptoms ; facilitation of lung inflammation absorption ; reduction of the risk of oxygen desaturation and the stabilization of abnormal fluctuation of oxygen saturation in the blood ; reduction in the dosage of glucocorticoid and antiviral agents (and therefore in their associated side-effects) and reduction of cost (treatment with TCM alone costs less than treatment with Western medicine alone). Introduction 3 Third level The experts noted that the data in the reports were inconclusive. An example of this is the clinical observation that the mortality rate is lower for the patients treated with integrated TCM and Western medicine than for those treated with Western medicine alone. As the diagnosis of SARS is very difficult to confirm, and some cases may be misdiagnosed, this could lead to a lower recorded mortality rate. In the prevention studies, the response rate to the questionnaires was only 40% among those subjects who had taken the prevention formula ; this was too low to enable an accurate assessment of its effects. In the study on convalescence, the comparison was made between only two groups, one treated with TCM and one with exercise. There was no comparison group that received neither treatment nor exercise programmes.
[...]
Discussion excerpts
[...]
We observed no adverse effects of treating SARS patients with TCM, but rather symptoms were improved. Some of the improvements may be related to decreased steroid usage. This observation suggests that TCM may have potential use in relieving the side-effects of steroid treatments. The need to provide TCM care for SARS patients created the first opportunity for TCM to be used at the ward level of public hospitals in Hong Kong SAR. It also marked the first step in the official recognition of TCM and in the functional integration of Western medicine and TCM in the public hospitals of Hong Kong SAR.

Excerpts mentioning Artemisia annua

Treatment for SARS with Traditional Chinese medicine

This treatment was developed by experts authorized by the Beijing Municipal Administration for TCM, and is recommended by this body.

Therapy with traditional Chinese medicine :

Prescription : Parched ephedra 5 g, almond 12 g, fossilia chitonis 45 g, Rhizoma Anemarrhenae 10 g, honeysuckle flower 15 g, Fructus Forsythiae 12 g, parched Fructus Gardeniae 12 g, Fructus Scutellariae 12 g, perilla leaf 10 g, Herba Artemisiae 15 g, Radices Puerarire 15 g, pseudostellaria root 15 g. To be decocted for oral administration ; each prescription is decocted into two bags (150 ml/bag) ; to be taken three times a day, one bag each time.
[...]
Dampness and heat in the liver channel : The herbal decoction for oral administration is SARS prescription 10 (Paris polyphylla Sm. Rhizoma Bistortae 20 g, Rhizoma Smilacis Glabrae 30 g, Herba Hedyotidis 15 g, herba of stringy stonecrop 15 g, Herba Artemisiae Annuae (15 g), Fructus Schizandrae 10 g, parched Atractylodes macrocephala 10 g, and three scorched herbs (scorched germinating barley, hawthorn fruit and medicated leaven) 30g) used in combination with intravenous drip of kuhuang injection or yinzhihuang injection.
[…]
Therapy with traditional Chinese medicine High-fever stage : 1 to 7 days after onset of the disease with high fever as the first and the most prominent symptom. Treatment focused on removing heat, repelling toxin and dispelling dampness and turbidity. SARS : Treatment using a combination of Traditional Chinese medicine and Western medicine 114 Regimen 1 : Fossilia Chitonis (45 g) (put in first), Rhizoma Anemarrhenae (15 g), Fructus Scutellariae (15 g), Rhizoma Atractylodis (10 g), Herba Artemisiae Annuae (15 g), Radix Paeoniae Rubra (15 g), Radix Bupleuri (10 g).
[…]
Dyspnoea and cough stage : 8 to 14 days after onset, characterized by severe dyspnoea and cough, fever and increasing shadows on lungs. Treatment focused on relieving dampness and fever and ventilating the lungs to relieve symptoms. Regimen 2 : Fructus Scutellariae (20 g), Diosoreae gracillimae (10 g), Rhizoma Coptidis (15 g), Faeces Bombycis (10 g), Trichosanthes Kirilowii (30 g), Herba Artemisiae Annuae (15 g), Semen Coicis (30 g), Flos Inulae (10 g, wrapped), Radix Curcumae (15 g), Radix Salviae Miltiorrhizae (30 g).
[…]
Prescription 3 For replenishing the vital essence and removing heat, used against deficiency of yin caused by the lingering of pathogenic factor : American ginseng (3 g), Radix Adenophorae Strictae (15 g), Radix Ophiopognis (12 g), Radix Bupleuri (9 g), Radix Scutellariae (12 g), mulberry leaf (15 g), Cortex Lycii Radicis (12 g), Herba Artemisiae (15 g), Rhizoma Phragmitis (15 g), Radix Angelicae Sinensis (9 g), Radix Paeoniae Alba (12 g), Rhizoma Pinelliae (9 g), roasted malt (15 g) and liu yi san (10 g).

Adjustment to individual symptoms

The following adjustments were made in response to specific symptoms. ♦ Plus Herba Artemisiae and chicken-bone herb for those with damaged liver functions or accompanied with increased level of cholerythrin ;

Zhang Jun-Feng, Tan Jian, Pu Qiang, Liu Ying-Hua, Liu Yue-Xue, He Kai-Ze
Study on the antiviral activities of condensed tannin of Artemisia annua L.
Natural Product Research 2004 ; 16 (4) : 307–11

Abstract in English but Full text in Chinese non available

Abstract :

Inhibitory effects of condensed tannin of Artemisia annua L.(CTA) on herpes simplex virus type 2(HSV-2) and HBeAg secretion in cultured HepG2.2.1.5 cell line were investigated. When the anti-HSV-2 activity of CTA was tested with acyclovir(ACV) as contrast drug, CC 50 of CTA and ACV were 6.84 mg/mL and 3.69 mg/mL, IC 50 were 0.162 mg/mL and 0.138 mg/mL respectively. The results showed CTA was as effective as the clinical drug-ACV. To study the anti-hepatitis B virus activity of CTA, the cytotoxicity to 2.2.1.5 cell line and inhibition of HBeAg secretion were tested. The results showed that CTA had slight cytotoxicity at 2.5 mg/mL and can distinctly inhibit the secretion of HBeAg in HepG2.2.1.5 cell line. All the results indicated that CTA maybe have a high selectivity index against HSV and HBV.

2005

Shi-you Li, Cong Chen, Hai-qing Zhang, Hai-yan Guo, Hui Wang, Lin Wang a,b , Xiang Zhang c , Shi-neng Hua, Jun Yu, Pei-gen Xiao, Rong-song Li, Xuehai Tan
Identification of natural compounds with antiviral activities against SARS-associated coronavirus
Antiviral Research 67 (2005) 18-23, © 2005 Elsevier B.V

Identification of natural compounds with antiviral activities against SARS-associated coronavirus

Abstract :

More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4 +/- 0.2 to 88.2 +/- 7.7 microg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7 +/- 1.2 nM. This compound has a CC50 value of 14980.0 +/- 912.0 nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.

Marta R. Romero, Thomas Efferth, Maria A. Serrano, Beatriz Castaño, Rocio I.R. Macias, Oscar Briz, Jose J.G. Marin,
Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an “in vitro” replicative system
Antiviral Research 68 (2005) 75–83

Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an “in vitro” replicative system

Abstract :

The antiviral effect against hepatitis B virus (HBV) of artemisinin, its derivative artesunate and other compounds highly purified from traditional Chinese medicine remedies, were investigated. HBV production by permanently transfected HepG2 2.2.15 cells was determined by measuring the release of surface protein (HBsAg) and HBV-DNA after drug exposure (0.01-100 microM) for 21 days. The forms of HBV-DNA released were investigated by Southern-blotting. Neutral Red retention test was used to evaluate drug-induced toxicity on host cells. The compounds were classified according to their potential interest as follows : (i) none : they had no effect on viral production (daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin) ; (ii) low : they were able to markedly reduce viral production, but also induced toxicity on host cells (berberine and tannic acid) or they had no toxic effect on host cells but only had a moderate ability to reduce viral production (curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin) ; (iii) high : they induced strong inhibition of viral production at concentrations at which host cell viability was not affected (artemisinin and artesunate). Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection.

2006

Romero Marta, Serrano Maria, Vallejo Marta, Efferth Thomas ; Alvarez, Marcelino ; Marin, Jose
Antiviral Effect of Artemisinin from Artemisia annua against a Model Member of the Flaviviridae Family, the Bovine Viral Diarrhoea Virus (BVDV)
Planta Medica 72(13):1169-74, November 2006

Antiviral Effect of Artemisinin from Artemisia annua against a Model Member of the Flaviviridae Family, the Bovine Viral Diarrhoea Virus (BVDV)

Abstract :

The antiviral activity versus flaviviruses of artemisinin, a safe drug obtained from Artemisia annua and commonly used to treat malaria, has been investigated using as an IN VITRO model bovine epithelial cells from embryonic trachea (EBTr) infected with the cytopathic strain Oregon C24V, of bovine viral diarrhoea virus (BVDV), which is a member of the Flaviviridae family. Antiviral activity was estimated by the degree of protection against the cytopathic effect of BVDV on host cells and by the reduction in BVDV-RNA release to the culture medium. To induce an intermediate cytopathic effect in non-treated cells, EBTr cells were first exposed to BVDV for 48 h and then incubated with virus-free medium for 72 h. Ribavirin and artemisinin (up to 100 microM) induced no toxicity in host cells, whereas a slight degree of toxicity was observed for IFN-alpha at concentrations above 10 U/mL up to 100 U/mL. Treatment of infected cells with IFN-alpha, ribavirin and artemisinin markedly reduced BVDV-induced cell death. A combination of these drugs resulted in an additive protective effect. These drugs induced a significant reduction in the production/release of BVDV virions by infected EBTr cells ; there was also an additive effect when combinations of them were assayed. These results suggest a potential usefulness of artemisinin in combination with current pharmacological therapy for the treatment of human and veterinary infections by flaviviruses.

2007

Yan CHEN, Jeff J. GUO, Daniel P HEALY, Siyan ZHAN
Effect of integrated traditional Chinese medicine and western medicine on the treatment of severe acute respiratory syndrome : A meta-analysis
Pharmacy Practice 2007 ; 5(1) : 1-9.

Effect of integrated traditional Chinese medicine and western medicine on the treatment of severe acute respiratory syndrome : A meta-analysis

Abstract

Background : Data regarding the treatment efficacy of integrative treatment of Traditional Chinese Medicine (TCM) and Western Medicine (WM) in treating patients with (SARS) are conflicting. The effects of integrative TCM/WM treatment have not been fully quantified.

Objectives : To systematically asses the treatment effects of integrated TCM with WM versus WM alone in patients with SARS, incorporating data from recently published studies.

Methods : A meta-analysis was conducted, using published randomized and nonrandomized controlled clinical studies that compared the treatment effects of integrative TCM/WM with WM alone from 2002 to 2006.The outcome measurements included mortality rate, cure rate, resolution of pulmonary infiltrate, use of corticosteroid, and time to defervescence. The effect sizes were presented as risk ratio (RR), rate difference (RD), and weighted mean difference (WMD).The pooled effect sizes were calculated by both fixed-effects and random-effects models.

Results : A total of 1,678 patients with a diagnosis of SARS were identified, including 866 patients from 16 randomized controlled studies and 812 patients from 8 nonrandomized controlled studies. There were no differences detected in mortality rate or cure rate between treatments. Compared with patients receiving WM treatment alone, patients receiving integrative treatment were more likely to have complete or partial resolution of pulmonary infiltrate (RD=0.18, 95%CI ; 0.07 to 0.30), lower average daily dosage (mg) of corticosteroid (WMD=-60.27, 95% CI ; -70.58 to -49.96), higher CD4+ counts (cells/uL) (WMD=167.96, 95% CI ; 109.68 to 226.24), and shorter time to defervescence (days) (WMD= -1.06, 95%CI ;-1.60 to -0.53).

Conclusions : The experience of integrative TCM/WM in the treatment of SARS is encouraging. The use of TCM as an adjunctive therapy in the treatment of SARS should be further investigated.

Wang S, Du QS, Zhao K, Li AX, Wei DQ, Chou KC.
Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy.
Amino Acids 2007 ; 33(1):129–35. 39.

Summary.

Recently Simmons et al. reported a new mechanism for SARS virus entry into target cells, where MDL28170 was identified as an efficient inhibitor of CTSL-meditated substrate cleavage with IC50 of 2.5 nmol=l. Based on the molecule fingerprint searching method, 11 natural molecules were found in the Traditional Chinese Medicines Database (TCMD). Molecular simulation indicates that the MOL376 (a compound derived from a Chinese medicine herb with the therapeutic efficacy on the human body such as relieving cough, removing the phlegm, and relieving asthma) has not only the highest binding energy with the receptor but also the good match in geometric conformation. It was observed through docking studies that the van der Waals interactions made substantial contributions to the affinity, and that the receptor active pocket was too large for MDL21870 but more suitable for MOL736. Accordingly, MOL736 might possibly become a promising lead compound for CTSL inhibition for SARS therapy.

Keywords : Severe acute respiratory syndrome (SARS) – MDL28170 – KZ7088 – Molecular simulation – Docking – Structural bioinformatics

Conclusion

The combination of the Traditional Chinese Medicine Database (TCMD) and the modern three dimensional drug design technique provides a powerful tool for new drug discovery and may find natural product drugs with high efficient and lower toxicity. The newly identified proteinase CTSL is an important target in drug design for therapeutic intervention of SARS-CoV infection. Because the function of CTSL is in the membrane fusion step, the inhibitors of CTSL may prevent the virus from entering the target cells. Therefore, it may be a better target than SARS-CoV Mpro. Eleven Chinese herb compounds are screened from TCMD based on the structure of template MDL28170. Among them MOL736 has the highest similarity and lowest binding energy. The compound MOL736 (chemical name Aurantiamide acetate) is derived from a Chinese medicine herb, Artemisia annua (Zhou et al., 2004). This plant is known as a herb medicine with many therapeutic efficacies, such as antitracheitis, relieving cough, removing the phlegm, relieving asthma and so on (Sheng et al., 2004). Therefore, it is a hopeful drug candidate against SARS.

2008

Efferth T, Romero MR, Wolf DG, Stamminger T, Marin. JJG, Marschall M. 
The antiviral activities of artemisinin and artesunate
Clin Infect Dis. 2008 ; 47:804-11.

The antiviral activities of artemisinin and artesunate

Abstract :

Traditional Chinese medicine commands a unique position among all traditional medicines because of its 5000 years of history. Our own interest in natural products from traditional Chinese medicine was triggered in the 1990s, by artemisinin-type sesquiterpene lactones from Artemisia annua L. As demonstrated in recent years, this class of compounds has activity against malaria, cancer cells, and schistosomiasis. Interestingly, the bioactivity of artemisinin and its semi synthetic derivative artesunate is even broader and includes the inhibition of certain viruses, such as human cytomegalovirus and other members of the Herpesviridae family (e.g.,herpes simplex virus type 1 and Epstein-Barr virus), hepatitis B virus, hepatitis C virus, and bovine viral diarrhea virus. Analysis of the complete profile of the pharmacological activities and molecular modes of action of artemisinin and artesunate and their performance in clinical trials will further elucidate the full antimicrobial potential of these versatile pharmacological tools from nature.

N.Q. Liu, F, Van der Kooy, R. Verpoorte
Artemisia afra : A potential flagship for African medicinal plants ?
South African Journal of Botany 75 (2009) 185–195

Artemisia afra : A potential flagship for African medicinal plants ?

Abstract :

The genus Artemisia consists of about 500 species, occurring throughout the world. Some very important drug leads have been discovered from this genus, notably artemisinin, the well known anti-malarial drug isolated from the Chinese herb Artemisia annua. The genus is also known for its aromatic nature and hence research has been focussed on the chemical compositions of the volatile secondary metabolites obtained from various Artemisia species. In the southern African region, A. afra is one of the most popular and commonly used herbal medicines. It is used to treat various ailments ranging from coughs and colds to malaria and diabetes. Although it is one of the most popular local herbal medicines, only limited scientific research, mainly focussing on the volatile secondary metabolites content, has been conducted on this species. The aim of this review was therefore to collect all available scientific literature published on A. afra and combine it into this paper. In this review, a general overview will be given on the morphology, taxonomy and geographical distribution of A. afra. The major focus will however be on the secondary metabolites, mainly the volatile secondary metabolites, which have been identified from this species. In addition all of the reported biological activities of the extracts derived from this species have been included as well as the literature on the pharmacology and toxicology. We aim at bringing together most of the available scientific research conducted on this species, which is currently scattered across various publications, into this review paper.

Keywords : Artemisia afra ; Traditional African Medicine ; Volatile secondary Metabolites

2009

Yang GE, Bao L, Zhang XQ, Wang Y, Li Q, Zhang WK, Ye WC
Studies on flavonoids and their antioxidant activities of Artemisia annua
Zhong Yao Cai. 2009 Nov ; 32(11) : 1683-6.

Full text in Chinese not available

Abstract :

To study the flavonoids and their antioxidant activities of Artemisia annua. Isolation and purification were carried out by silica gel and Sephadex LH-20 column chromatographies. Compounds were identified by physicochemical properties and spectral analysis, then their antioxidant activities were evaluated by ORAC assay. Five flavonoids were isolated from the plant. Their structures were identified as 5-hydroxy-3,7,4’-trimethoxyflavone(1), 5-hydroxy-6,7,3’,4’-tetramethoxyflavonol (2), blumeatin (3), 5, 4’-dihydroxy-3,7,3’-trimethoxyflavone (4) and quercetin (5), respectively. Compounds 1-5 could slow up the attenuation rate of the fluorescence induced by AAPH. Compounds 1-3 are isolated from the plant for the first time. Compounds 1-5 all possess the potential antioxidant activities.

2010

J.F.S. Ferreira, Dave Luthria, Tomikazu Sasaki, Arne Heyerick,
Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer
Molecules 2010, 15, 3135-3170

Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer

Abstract :

Artemisia annua is currently the only commercial source of the sesquiterpene lactone artemisinin. Since artemisinin was discovered as the active component of A. annua in early 1970s, hundreds of papers have focused on the anti-parasitic effects of artemisinin and its semi-synthetic analogs dihydroartemisinin, artemether, arteether, and artesunate. Artemisinin per se has not been used in mainstream clinical practice due to its poor bioavailability when compared to its analogs. In the past decade, the work with artemisinin-based compounds has expanded to their anti-cancer properties. Although artemisinin is a major bioactive component present in the traditional Chinese herbal preparations (tea), leaf flavonoids, also present in the tea, have shown a variety of biological activities and may synergize the effects of artemisinin against malaria and cancer. However, only a few studies have focused on the potential synergistic effects between flavonoids and artemisinin. The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution of the World Health Organization to support artemisinin-based combination therapies (ACT), instead of the previously used monotherapy with artemisinins. In this critical review we will discuss the possibility that artemisinin and its semi-synthetic analogs might become more effective to treat parasitic diseases (such as malaria) and cancer if simultaneously delivered with flavonoids. The flavonoids present in A. annua leaves have been linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body, but also have been linked to a beneficial immunomodulatory activity in subjects afflicted with parasitic and chronic diseases.
Keywords : Artemisia annua ; artemisinin ; flavonoids ; antimalarial, anticancer ; synergism.

2011

Keivan Zandi, Boon-Teong Teoh, Sing-Sin Sam, Pooi-Fong Wong, Mohd Rais Mustafa and Sazaly AbuBakar
Antiviral activity of four types of bioflavonoid against dengue virus type-2
Virology Journal 2011, 8:560

Antiviral activity of four types of bioflavonoid against dengue virus type-2

Abstract :

Background : Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC 50 ) to inhibitory concentration 50 (IC 50 ) for each compound.

Results : The half maximal inhibitory concentration (IC 50 ) of quercetin against dengue virus was 35.7 μg mL -1 when it was used after virus adsorption to the cells. The IC 50 decreased to 28.9 μg mL -1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL -1 , respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC 50 = 168.2 μg mL -1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC 50 = 142.6 μg mL -1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL -1 ) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin.

Conclusion : Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and hesperetin showed minimal to no significant inhibition of DENV-2 virus replication. These findings, together with those previously reported suggest that select group of bioflavonoids including quercetin and fisetin, exhibited significant inhibitory activities against dengue virus. This group of flavonoids, flavonol, could be investigated further to discover the common mechanisms of inhibition of dengue virus replication.

Keywords : Antiviral, Dengue virus, Flavonoid, Quercetin, Naringin, Daidzein, Hesperetin

Conclusion : Les résultats de l’étude suggèrent que seule la quercétine a démontré des activités inhibitrices anti-DENV-2 significatives. D’autres bioflavonoïdes, dont la daidzéine, la naringine et l’hespérétine, ont montré une inhibition minimale ou nulle de la réplication du virus DENV-2. Ces résultats, ainsi que ceux rapportés précédemment, suggèrent que certains groupes de bioflavonoïdes, dont la quercétine et la fisétine, présentent des activités inhibitrices significatives contre le virus de la dengue. Ce groupe de flavonoïdes, les flavonols, pourrait faire l’objet de recherches plus approfondies afin de découvrir les mécanismes communs d’inhibition de la réplication du virus de la dengue.

MK Karamoddini, SA Emami, MS Ghannad, A Sahebcar.
Antiviral activities of aerial subsets of Artemisia species against Herpes Simplex virus type 1 (HSV1) in vitro
Asian Biomedicine vol 5-1, 2011, 63-6

Antiviral activities of aerial subsets of Artemisia species against Herpes Simplex virus type 1 (HSV1) in vitro

Abstract :

Background : Drug resistance to current anti-herpetic drugs has been increasingly reported. Therefore, there is a need for finding new antiviral agents, in particular from natural sources.

Objective : In the present study, antiviral activity of subset extracts obtained from aerial parts of Artemisia including A. incana, A. chamaemelifolia, A. campesteris, A. fragrans, A. annua, A. vulgaris, and A. persica were investigated against Herpes Simplex type I (HSV1).

Methods : Different concentrations of extracts (400, 200, 100, 50, 25, 12.5, 6.25, and 3.125 μg/mL) were obtained from subset of each plant separately, and used against KOS strain of HSV1 in HeLa cells. After 24 hours incubation, tetrazolium dye (MTT), was added. The dye absorption by viable cells was measured and compared to the positive control (extract-untreated cells) and acyclovir (as anti-viral agent).

Results : The extracts obtained from A. annua had the highest antiviral activity while those of A. chamaemelifolia showed the lowest activity.

Conclusion : Subset extracts of A. annua may be an appropriate candidate for further development of anti HSV1 infection.

Keywords : Antivirals, Artemisia, asteraceae, herpes simplex

2012

Andrea Lubbe, Isabell Seibert, Thomas Klimkait, Frank van der Kooy.
Ethnopharmacology in overdrive : The remarkable anti-HIV activity of Artemisia annua
Journal of Ethnopharmacology (2012) JEP-7371

Ethnopharmacology in overdrive : The remarkable anti-HIV activity of Artemisia annua

Abstract

Ethnopharmacological relevance : Artemisia annua contains the well-known antimalarial compound artemisinin, which forms the backbone of the global malaria treatment regime. In African countries a tea infusion prepared from Artemisia annua has been used for the treatment of malaria only for the past 10-20 years. Several informal claims in Africa exist that the Artemisia annua tea infusions are also able to inhibit HIV. Since HIV is a relatively newly emerged disease, the claims, if substantiated, could provide a very good example of "ethnopharmacology in overdrive". The objective of this study was to provide quantitative scientific evidence that the Artemisia annua tea infusion exhibits anti-HIV activity through in vitro studies. A second objective was to determine if artemisinin plays a direct or indirect (synergistic) role in any observed activity. This was done by the inclusion of a chemically closely related species, Artemisia afra, known not to contain any artemisinin in our studies.

Materials and methods : Validated cellular systems were used to test Artemisia annua tea samples for anti-HIV activity. Two independent tests with different formats (an infection format and a co-cultivation format) were used. Samples were also tested for cellular toxicity against the human cells used in the assays.
Results : The Artemisia annua tea infusion was found to be highly active with IC(50) values as low as 2.0 μg/mL. Moreover we found that artemisinin was inactive at 25 μg/mL and that a chemically related species Artemisia afra (not containing artemisinin) showed a similar level of activity. This indicates that the role of artemisinin, directly or indirectly (synergism), in the observed activity is rather limited. Additionally, no cellular toxicity was seen for the tea infusion at the highest concentrations tested.

Conclusion : This study provides the first in vitro evidence of anti-HIV activity of the Artemisia annua tea infusion. We also report for the first time on the anti-HIV activity of Artemisia afra although this was not an objective of this study. These results open the way to identify new active pharmaceutical ingredients in Artemisia annua and thereby potentially reduce the cost for the production of the important antimalarial compound artemisinin.

2013

Frank Van der Kooy
Reverse Pharmacology and Drug Discovery : Artemisia annua and Its Anti-HIV Activity
In : Aftab T., Ferreira J., Khan M., Naeem M. (eds) Artemisia annua - Pharmacology and Biotechnology. Springer, Berlin, Heidelberg, 27 November 2013, pp 249-267

Reverse Pharmacology and Drug Discovery : Artemisia annua and Its Anti-HIV Activity

Abstract

There are various ways in which new drugs can be developed. One approach is in silico drug design based on our existing knowledge of the biology of a specific disease and the specific target site binding chemistry. Based on this knowledge, a range of molecules will be designed and synthesised after which they will be tested in in vitro bioassays for activity and toxicity. The best candidates, called lead compounds, will then be “fine-tuned” by chemical derivatisation in order to improve their activity and/or to reduce their toxicity. Lead compounds are then tested in various animal models before entering clinical trials in people. Another approach is to screen a large number of biological samples (plants, bacteria and fungi) for activity against a specific disease. Any active extract, consisting of many compounds, will be fractionated by chromatographic techniques, and each fraction will be tested for in vitro activity. Active fractions will again be fractionated until the active compound is identified. This process, also called bioguided fractionation, can go through a number of fractionation cycles before the active compound is identified. The active compound will be chemically derivatised in order to improve its properties before in vivo animal studies will be conducted. Based on these test results, the most promising lead compounds will then be tested in clinical trials in people. There are however a number of shortcomings with both approaches. It is expensive, time consuming, makes use of in vitro bioassays and it suffers from a very low success rate. Due to these shortcomings, it is currently estimated that the development of one new drug costs around $1–1.5 billion, simply because so many lead compounds fail during clinical trials. Keeping these high costs in mind, one would think that all registered drugs are effective and importantly non-toxic. Unfortunately, this is not the case, as there are a number of drugs currently on the market that are causing severe side effects and whose efficacy should be questioned. This holds true particularly for cancer chemotherapeutics. It was estimated that cancer chemotherapy improves the average 5-year survival rate of patients (for all cancer types) by only 2 % (Morgan et al. 2004). Another relatively unknown fact is that each year, 200,000 people die in the EU due to adverse drug reactions (all types of drugs), highlighting the severe shortcomings of the drug development and drug licensing pipelines (Archibald and Coleman 2012). To put this into perspective, there are a large number of drugs that work perfectly well and are safe to use, but we have to concede that our approach to drug discovery and our overall approach to health care suffers from some major problems.

Keywords : Medicinal Plant Chlorogenic Acid Bovine Viral Diarrhoea Virus Artemisinin Derivative Vitro Bioassay

Xiaoxin X. Zhu, Lan Yang, Yujie J. Li, Dong Zhang, Ying Chen, Petra Kostecká, Eva Kmoníèková, Zdenìk Zídek
Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis
Pharmacological Reports, 2013, 65, 410-420 ISSN 1734-1140

{Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis

Abstract :

Background : In addition to recognized antimalarial effects, Artemisia annua L.(Qinghao) possesses anticancer properties. The underlying mechanisms of this activity are unknown. The aim of our experiments was to investigate the effects of distinct types of compounds isolated from A. annua on the immune-activated production of major mediators of angiogenesis playing a crucial role in growth of tumors and formation of metastasis.

Methods : Included in the study were the sesquiterpene lactones artemisinin and its biogenetic precursors arteannuin B and artemisinic acid. The semi-synthetic analogue dihydroartemisinin was used for comparative purposes. The flavonoids were represented by casticin and chrysosplenol D, the coumarin type of compounds by 4-methylesculetin. Their effects on the lipopolysaccharide (LPS)-induced in vitro production of nitric oxide (NO) were analyzed in rat peritoneal cells using Griessre agent. The LPS-activated production of prostaglandin E2 (PGE2) and cytokines (VEGF, IL-1b, IL-6 and TNF-a) was determined in both rat peritoneal cells and human peripheral blood mononuclear cells using ELISA.

Results : All sesquiterpenes (artemisinin, dihydroartemisinin, artemisinic acid, arteannuin B) significantly reduced production of PGE2 . Arteannuin B also inhibited production of NO and secretion of cytokines. All NO, PGE2 andcytokines were suppressed by flavonoids casticin and chrysosplenol D. The coumarin derivative, 4-methylesculetin, was ineffective to change the production of any of these factors.

Conclusions : The inhibition of immune mediators of angiogenesis by sesquiterpene lactones and flavonoids may be one of the mechanisms of anticancer activity of Artemisia annua L.

Key words : Artemisia annua L., nitric oxide, prostaglandins, cytokines, angiogenic factors

2014

Liang-Tzung Lin, Wen-Chan Hsu, Chun-Ching Lin
Antiviral Natural Products and Herbal Medicines
Journal of Traditional and Complementary Medicine, 2014, Vo1. 4, No. 1, pp. 24-35

Antiviral Natural Products and Herbal Medicines

Abstract :

Viral infections play an important role in human diseases, and recent outbreaks in the advent of globalization and ease of travel have underscored their prevention as a critical issue in safeguarding public health. Despite the progress made in immunization and drug development, many viruses lack preventive vaccines and efficient antiviral therapies, which are often beset by the generation of viral escape mutants. Thus, identifying novel antiviral drugs is of critical importance and natural products are an excellent source for such discoveries. In this mini‑review, we summarize the antiviral effects reported for several natural products and herbal medicines.

Key words : Antiviral, Drug development, Herbal medicines, Natural products

Alka Singh, Bendangchuchang Longchar, Feroz Khan, Alka Singh, Sunita Jindal, Vikrant Gupta
Over expression of Artemisia annua sterol C-4 methyl oxidase gene, AaSMO1, enhances total sterols and improves tolerance to dehydration stress in tobacco
Plant Cell Tissue and Organ Culture 121(1) : 167-181, April 2014

Over expression of Artemisia annua sterol C-4 methyl oxidase gene, AaSMO1, enhances total sterols and improves tolerance to dehydration stress in tobacco

Abstract :

Biosynthesis of sterols is a multistep process in higher plants where the precursor cycloartenol gets converted into functional phytosterols after removal of two methyl groups at C-4 by an enzyme complex involving a sterol C-4 methyl oxidase (SMO). We identified and cloned a cDNA from Artemisia annua designated as AaSMO1 showing similarity to SMO. The cDNA predicted to encode a polytopic protein with characteristic histidine-rich motifs and an ER retrieval signal. GFP-AaSMO1 fusion protein was localized in endoplasmic reticulum of transformed protoplast and onion epidermal cells. AaSMO1 expression was drastically induced upon osmotic/dehydration stress and its promoter showed the presence of abscisic acid responsive element. Transgenic tobacco plants ectopically overexpressing AaSMO1 were raised, and various biochemical and physiological analyses of transgenics revealed increased total sterol, better germination and growth in subsequent generations. They also exhibited reduced sensitivity towards osmotic/dehydration stress which may be attributed to enhanced SMO1 activity. Our studies demonstrated that apart from acting as phytohormones, plant sterols also participate in providing capability to plants for improved growth and adaptation during stress conditions. AaSMO1 can be used as an excellent candidate for generating dehydration/drought tolerant plants.

Keywords : Plant sterols, Sub-cellular localization, AaSMO1, Dehydration stress, RT-qPCR

2015

Islamuddin M, Chouhan G, Farooque A, Dwarakanath BS, Sahal D, Afrin F.
.
PLoS Negl Trop Dis 2015 ; 9(1) : e3321

Wenjiao Wu, Richan Li, Xianglian Li, Jian He, Shibo Jiang, Shuwen Liu, and Jie Yang
Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry
Viruses, Volume : 8, Issue : 1, pp. 6, Dec 2015

Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

Abstract :

Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.

Keywords : entry inhibitor, hemagglutinin, influenza A virus, quercetin

Christoph Reiter, Tony Fröhlich, Lisa Gruber, Corina Hutterer, Manfred Marschall, Cornelia Voigtländer, Oliver Friedrich, Barbara Kappes, Thomas Efferth, Svetlana B. Tsogoeva
Highly potent artemisinin-derived dimers and trimers : Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities
Bioorganic & Medicinal Chemistry 23 (2015) 5452–5458

Highly potent artemisinin-derived dimers and trimers : Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities

Abstract :

New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodium falciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC 50 of 2.6 nM) possess superior anti-malarial activity compared with its parent compound artesunic acid (3) (IC 50 of 9.0 nM). Dimer 5 and trimers 6 and 7 display superior potency against both leukemia cell lines (IC 50 up to 0.002 l M for CCRF-CEM and IC 50 up to 0.20 l M for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC 50 1.61 l M for CEM/ADR5000). With respect to anti-HCMV activity, trimer 6 is the most efficient hybrid (IC 50 0.04 l M) outperforming ganciclovir (IC 50 2.6 l M), dihydroartemisinin (IC 50 >10 l M) and artesunic acid (IC 50 3.8 l M).

Keywords : Artemisinin-derived hybrids, Artemisinin-derived dimers, Artemisinin-derived trimers, Antimalarial activity, Anticancer activity, Antiviral activity

Shi-you Li ; Cong Chen ; Hai-qing Zhang ; Hai-yan Guo ; Hui Wang ; Lin Wang ; Xiang Zhang ; Shi-neng Hua ; Jun Yu ; Pei-gen Xiao ; Rong-song Li ; Xuehai Tan
Identification of natural compounds with antiviral activities against SARS‐associated coronavirus.
Antiviral Research, 67(1), 18–23. 10.1016/j.antiviral.2005.02.007

Identification of natural compounds with antiviral activities against SARS-associated coronavirus

Abstract :

More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndromeassociated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of the extracts, Lycoris radiata, Artemisia annua, Pyrrosia lingua, and Lindera aggregata exhibited significant inhibition effects on virus-induced virus-induced cytopathic effect when SARS-CoV strain BJ001 was used in screening. The inhibition effects of all four natural product samples showed dose-dependent patterns.. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7±1.2 nM. This compound has a CC50 value of 14980.0±912.0nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.

Keywords : Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) ; Drug screening ; Natural products ; Lycorine ; Lycoris radiata herb

2017

Eun Ji Kim, Guen Tae Kim, Bo Min Kim, Eun Gyeong Lim, Sang-Yong Kim and Young Min Kim
Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells
Complementary and Alternative Medicine (2017) 17:236

Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells

Abstract :

Background : The extracts from Artemisia annua Linné (AAE) has been known to possess various functions including anti-bacterial, anti-virus and anti-oxidant effects. However, the mechanism of those effects of AAE is not well known. Pursuantly, we determined the apoptotic effects of extract of AAE in HCT116 cell. In this study, we suggested that AAE may exert cancer cell apoptosis through TEN/PDK1/Akt/p53signal pathway and mitochondria-mediated apoptotic proteins.

Methods : We measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, Annexin V-PI staining, Mitopotential assay, immunofluorescence (IF) and Western blotting. Accordingly, our study showed that AAE treatment to HCT116 cells resulted in inhibition of PDK1, Akt, MDM2, Bcl-2, and pro-caspase 3 as well as activation of PTEN, p53-upregulated modulator of apoptosis (PUMA), Bax and Bak expression. Also we measured in vivo assay that xenograft model, H&E assay, TUNEL assay and IHC.

Results : AAE induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through PTEN/p53-independent manner. AAE inhibit cell viability and increase LDH release in HCT116 colon cancer cell. Also, AAE increase apoptotic bodies, caspase −3,7 activation and reduces mitochondria membrane potential. AAE regulates cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane in an Immunofluorescence staining and increase PTEN and p53 expression in an in vivo tumor xenograft model. To elucidate the role of the PTEN/p53/PDK1/Akt signal pathways in cancer control, we conditionally inactivated PTEN/p53/PDK1/Akt signal pathways. We used inhibitors of PTEN, p53, PDK1, Akt. In consequence, these results indicate that AAE induced apoptosis by means of a mitochondrial event through the regulation of proteins such as Bax, Bak and cytochrome c in PDK1/Akt signaling pathways via PTEM/p53-independent manner.

Conclusions : We confirmed the apoptotic effect of extracts of AAE by Modulating PTEN/p53/PDK1/Akt/Signal Pathways through PTEN/p53-independent pathwaysin HCT116 colon cancer cell.

Keywords : Phosphatase and tensin homolog (PTEN), p53-independent manner, Artemisia annua Linné, Apoptosis,
HCT116 colon cancer cell

2019

Wenwen Dai, Jinpeng Bi, Fang Li, Shuai Wang, Xinyu Huang, Xiangyu Meng, Bo Sun, Deli Wang, Wei Kong, Chunlai Jiang and Weiheng Su
Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
Viruses, 2019

Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice

Abstract :

Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications ; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures ; however, to date, there are no reported data on their effects in animal models. In this study, weconfirmedthe in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in new born mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development.

Keywords : enterovirus 71 ; flavonoid ; isorhamnetin ; antiviral efficacy ; inhibition of cytopathic effects ; survival rate

2020

Zhang, T., Zhang, Y., Jiang, N. et al.
Dihydroartemisinin regulates the immune system by promotion of CD8+ T lymphocytes and suppression of B cell responses.
Sci. China Life Sci. 63, 737–749 (2020). https://doi.org/10.1007/s11427-019-9550-4

Abstract

Artemisia annua is an anti-fever herbal medicine first described in traditional Chinese medicine 1,000 years ago. Artemisinin, the extract of A. annua, and its derivatives (dihydroartemisinin (DHA), artemether, and artesunate) have been used for the treatment of malaria with substantial efficacy. Recently, DHA has also been tested for the treatment of lupus erythematosus, indicating that it may function to balance the immune response in immunocompromised individuals. In the present study, the regulatory effect of artemisinin on the murine immune system was systematically investigated in mice infected with two different protozoan parasites (Toxoplasma gondii and Plasmodium berghei). Our results revealed that the mouse spleen index significantly increased (spleen enlargement) in the healthy mice after DHA administration primarily due to the generation of an extra number of lymphocytes and CD8+ T lymphocytes in both the spleen and circulation. DHA could increase the proportion of T helper cells and CD8+ T cells, as well as decrease the number of splenic and circulatory B cells. Further, DHA could reduce the production of proinflammatory cytokines. Our study revealed that apart from their anti-parasitic activity, artemisinin and its derivatives can also actively modulate the immune system to directly benefit the host.

Tu Youyou
Études sur les actions pharmacologiques de l’ Artemisia annua. Action antivirale
Extrait [Chapitre 6] de Youyou Tu, Prix Nobel de médecine. De Artemisia annua L. aux artémisinines. La découverte et le développement des artémisinines et des agents antipaludiques, QuintSciences, ECP Sciences, Chemical Industry Press
2019 Chemical Industry Press, published by Elsevier Inc., with Chemical Industry Press, in association with the B&R Book Program.

« 3.3 Action antivirale

Qian et al. [18] ont découvert dans un test d’infection par un embryon de poulet que l’artémisinine pouvait inhiber le virus de la grippe, mais ne tuait pas le virus. En 2005, Romero et al. [24] ont signalé l’action de l’artémisinine contre le virus de l’hépatite B.
Dans les laboratoires, il a été constaté que l’extrait aqueux de l’A. annua est actif contre le virus de l’herpès et le virus de l’hépatite B in vitro ; en utilisant des techniques de traçage d’activité, l’on constate que l’ingrédient antiviral est le tanin condensé. Une étude in vitro a été menée pour étudier l’activité anti-HSV-2 et anti-HBV d’un tanin condensé (CTA) isolé à partir de l’extrait aqueux de l’A. annua. Les résultats ont montré que le CTA avait une activité anti-HSV-2 considérable ; le CC 50 du comparateur positif, l’aciclovir (ACV) et le CTA étaient de 6,84 et 3,69 mg/ml, respectivement ; la CI 50 était de 0,162 et 0,138 mg/ml, respectivement, indiquant que le CTA est moins cytotoxique que le VCA, alors que les deux composés ont une activité antivirale équivalente. Selon les résultats de culture de cellules HepG2.2.1.5 dans des milieux contenant du CTA, le CTA a montré une cytotoxicité légère à 2,5 mg/ml et une action inhibitrice considérable contre l’AgHBe exprimé par les cellules HepG2.2.1.5 à 0,156 à 2,5 mg/ml et a le taux d’inhibition de l’AgHBe de 90,45 % au 12 e jour de la culture à 0,625 mg/mL, indiquant que le CTA a une activité anti-VHB potentielle [25].

Références citées :

[18] Qian RS , Li ZL , Yu JL , et al. Immunological and anti-viral actions of artemisinin. J Tradit Chin Med 1981 ; 22 ( 5 ) : 462 – 6 .
[24] Romero MR , Eferth T , Serrano MA , et al. Efect of artemisinin/artesunate as inhibitors of hepatitis B virus pro-duction in an “in vitro” replicative system . Antiviral Res 2005 ; 68 ( 2 ) : 75 – 83 .
[25] Zhang JF , Tan J , Pu Q , et al. A study on antiviral activity of Condensed Tannin of Artemisia annua . Res Dev Nat Prod 2004 ; 16 ( 4 ) : 307 – 11.. »

Editorial board
Redeploying plant defences
Nature Plants, volume 6, 177, 2020

Redeploying plant defences

Journal Editorial

Excerpt :

« Anti-viral herbal medicines have been used in many historic epidemics, for example the previous two coronavirus outbreaks (SARS-CoV in 2013 and MERS-CoV in 2012), seasonal epidemics caused by influenza viruses and dengue virus. Extracts from Lycoris radiate, Artemisia annua and Lindera aggregate, and the natural products isolated from Isatis indigotica, Torreya nucifera and Houttuynia cordata, showed anti-SARS effects 1–5. The plant flavone baicalein can prevent dengue virus entry into the host and inhibit post-entry replication 6 . Additionally, natural products from Pelargonium sidoides roots and dandelion have anti-influenza activities, as they inhibit virus entry and key viral enzyme activities.

Like chloroquine phosphate, these herbal medicines are generally not highly potent and thus cannot be regarded as a cure. Nevertheless, as a complementary treatment they can elevate recovery rates when combined with other treatments. In an emergency like the current COVID-19 outbreak, drugs like remdesivir — an experimental drug developed against Ebola and recently held up by WHO Assistant Director-general Bruce Aylward as the only “drug right now that we think may have real efficacy” — take time to pass clinical trials, but readily available herbal medicines and natural products with proven safety can buy time as a first line of defence.

Plants are important not only for food but also for medicine. Understanding the taxonomy, ecology and conservation of herbs, as well as the pathways of secondary metabolite synthesis, is important for drug development. Investing in research into ethnobotany, phytochemistry, plant physiology and ecology will be vital in protecting the global population from current and future pandemics. »

Yang, Y., Islam, M. S., Wang, J., Li, Y. Chen, X.
Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2) : A Review and Perspective
International Journal of. Biological Sciences. 16, 1708–1717 (2020).

Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2) : A Review and Perspective

Abstract :

Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.

Key words : SARS-CoV-2, Traditional Chinese Medicine (TCM), coronavirus pneumonia.

Faiz Ul Haq, Muhammad Roman, Kashif Ahmad, Saeed Ur Rahman, Syed Murtaza Ali Shah, Naveed Suleman, Sami Ullah, Iftekhar Ahmad, Wajahat Ullah
Short communication : « Artemisia annua : Trials are needed for COVID-19 »
Phytother Res . 2020 Oct ;34(10):2423-2424. doi : 10.1002/ptr.6733. Epub 2020 May 27.

Abstract

In December 2019, a number of pneumonia cases associated with 2019 novel coronavirus occurred in Wuhan, China. Later taxonomist name the virus SARS-CoV-2 and disease called COVID-19. No approved vaccine or treatment are available for this virus. Current technical guide is related to address therapeutic option for SARSCoV-2. COVID-19 is great challenge for scientist across the globe. Bioactive compound present in Artemisia annua against, hepatitis B virus, bovine viral diarrhea virus, and Epstein–Barr virus. A. annua have shown significant activity against SARS coronavirus that occur in 2002. This agent is cheap and easily available and will be of great value if they have efficacy against SARS-CoV-2. Scientific attention is needed toward this agent to address for the treatment of COVID-19.

Keywords : Artemisia annua, bioactive compound, coronavirus : antiviral agents : COVID-19, SARS-CoV-2

National Health Commission & State Administration of Traditional Chinese Medicine
Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)
(Released on March 3, 2020)

Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)

Excerpt :

4.2.2 Mild cases

4.2.2.1 Cold dampness and stagnation lung syndrome

Clinical manifestations : fever, fatigue, sore body, cough, expectoration, chest tightness, suffocation, loss of appetite, nausea, vomiting, sticky stools. Tongue has thin fat tooth mark or is faint red, and the coating is white thick rot or white greasy and the pulse is moisten or slippery.

Recommended prescription : Raw ephedra 6g, raw gypsum 15g, almond 9g, loquat 15g, gardenia 15g, Guanzhong 9g, Dilong 15g, Xu Changqing 15g, Huoxiang 15g, Peilan 9g, Cangzhu 15g, Yunling 45g, Atractylodes 30g, Jiao Sanxian 9g each , Magnolia 15g, betel coconut 9g, yarrow fruit 9g, ginger 15g.

Suggested use : one dose daily, boiled with 600ml water, take it three times at morning, noon and evening before meal.

4.2.2.2 Dampness and heat-accumulation lung syndrome

Clinical manifestations : low or no fever, slight chills, fatigue, heavy head and body, muscle soreness, dry cough, low phlegm, sore throat, dry mouth, do not want to drink more, or accompanied by chest tightness, no sweat or sweating, Or vomiting and loss of appetite, diarrhea or sticky stool. The tongue is reddish, and the coating is white, thick and greasy or thin yellow, and the pulse is slippery or sloppy.

Recommended prescription : Betel nut 10g, apple 10g, Magnolia 10g, Zhimu 10g, Scutellaria baicalensis 10g, Bupleurum 10g, red peony 10g, forsythia 15g, Artemisia annua 10g (decocted later), 10g of green leaves, 10g of green leaves, 5g of raw licorice.

Suggested use : one dose daily, boiled with 400ml water, take it twice at morning and evening.

4.2.3 Moderate cases

4.2.3.1 Dampness and stagnation lung syndrome

Clinical manifestations : fever, low cough and sputum, or yellow sputum, suffocation, shortness of breath, bloating, and constipation. The tongue is dark red and fat ; the coating is greasy or yellow and the pulse is slippery or stringy.

Recommended prescription : raw ephedra 6g, bitter almond 15g, raw gypsum 30g, raw coix seed 30g, grass root 10g, patchouli 15g, Artemisia annua 12g, Polygonum cuspidatum 20g, verbena 30g, dried reed root 30g, gardenia 15g 15g of orange red, 10g of raw licorice.

Suggested use : one dose daily, boiled with 400ml water, take it twice at morning and evening.

Siti Khaerunnisa, Hendra Kurniawan, Rizki Awaluddin, Suhartati Suhartati, Soetjipto Soetjipto
Potential Inhibitor of COVID-19 Main Protease (M pro ) from Several Medicinal Plant Compounds by Molecular Docking Study
Preprint, posted on 13 March 2020

Potential Inhibitor of COVID-19 Main Protease (M pro) from Several Medicinal Plant Compounds by Molecular Docking Study

Abstract :

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (M pro ), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 M pro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 M pro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and luteolin-7-glucoside, demethoxycurcumin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 M pro inhibitors. However, further research is necessary to investigate their potential medicinal use.

Keywords : COVID-2019 ; M pro ; 6LU7 ; Medicinal Plant Compounds ; Docking

Shahrajabian MH, Sun W, Shen H, Cheng Q
Chinese herbal medicine for SARS and SARS-CoV-2 treatment and prevention, encouraging using herbal medicine for COVID-19 outbreak
May 2020, Acta Agriculturae Scandinavica, Section B- Soil & Plant Science. https://doi.org/10.1080/09064710.2020.1763448

Abstract

Chinese herbs and plants have been used as traditional medicine, immune system booster for human being for thousands of years in China and other parts of Asia. Seven coronaviruses are known to infect humans, three of them are serious which are SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome), and SARS-CoV-2 (Covid-19). In this minireview article, we have mentioned the key role some of the most important plants with antiviral activities and herbs against SARS and SARS-CoV-2 on the basis of traditional Chinese medicine.

Conclusion

Traditional Chinese medicine (TCM) has a long history which is formed by summarising the precious experience of understanding life, maintaining health and fighting diseases accumulated in daily life, production and medical practices. Extracts from Artemisia annua, Lycoris radiate, Lidera aggregate, Isatis indigotica, Torreya nucifera and Houttuynia cordata showed anti-SARS effects. Extract of Pelargonium sidoides root and dandelion also have anti-influenza activities and they can inhibit virus entry and key viral enzyme activities. Licorice root has been in used in both traditional Chinese and Indian medicine for eons especially for respiratory ailments and diseases including pneumonia. Some other suggested herbs from TCM which use to treat and prevent coronavirus are Radix astragali (Huangqi), Radix glycyrrhizae (Ganacao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Fructus forsythia (Lianqiao). Qingfei Paidu decoction (QPD) is considered because of high efficacy contain Ephedrae Herba, Glycyrrhizae Radix et Rhizoma Praeprata cum Melle, Armeniacae Semen Amarum, Gypsum Fibrosum, Cinnamomi Ramulus, Alismatis Rhizoma, Polyporus, Astractylodis Macrocephalae Rhizoma, Poria, Bupleuri Radix, Scutellariae Radix, Pinelliae Rhizoma Praepratum cum Zingibere et Alumine, Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Farfarae Flos, Belamcandae Rhizoma, Asari Radix et Rhizoma, Dioscoreae Rhizoma, Aurantii Fructus Immaturus, Citri Reticulatae Pericarpium and Pogostemonis Herbal. Combining traditional Chinese medicine andchemical medicines may give better results, but it is better pharmacologists separate active pharmaceutical ingredients and identify explicit targets. The compounds extracted from A. annua, L. radiate, P. lingua, and L aggregate have been identified to show antiviral against SARS-CoV which ; but it may need to be tested for SARS-Covid-2. The compounds of Houttuynia cordata contribute to the superior antiviral efficacy of EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo, and it has great potential for the development of antiviral agents against coronavirus infection ; furthermore, three of its constituent flavonoids against murine coronavirus are quercetin, auercitrin and ruitn. Radix astragali (Huangqi), Glycrrihizae Radix Et Rhizoma (Ganacao), Radix saposhnikoviae (Fangfen), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), Fructus forsythia (Lianqiao), Atractylodis Rhizoma (Cangzhu), Radix platycodonis (Jiegeng), Pogostemonis Herba (Huoxiang), Cyrtomium fortune J. Sm. (Guanzhong), Perillae Folium (Zisuye), Rhizoma phragmitis (Lugen), Glehniae Radix (Shashen), Citri Reticulatae Pericarpium (Chenpi), Ophiopogonis Radix (Maidong), Eupatorii Herba (Peilan), Folium isatidis (Banlangen), Coicis Semen (Yiyiren), and Folium mori (Sangye) are the most common herbs in preventive formulae for COVID-19. Some important chemical constituents in traditional herbs which can consider them in fight against COVID-10 are Betulinic acid, Coumaroyltyramine, Cryptotanshinone, Desmethoxyreserpine, Dihomo-γ-linolenic acid, Dihydrotanshinone I, Kaempferol, Lignan, Moupinamide, N-cis-feruloyltyramine, Quercetin, Sugiol and Tanshinone IIa. The most important herbal formulae for COVID-19 were herbal formula of Shen Fu Tang with Su He Xiang Pill or Angong Niuhuang Pill in the severe stage and the combined formula of Xiang Sha Liu Junzi Tang and Li Zhong Pill in the recovery stage ; furthermore, Angong Niuhuang Pill, Zhi Bao Dan, Zi Xue San, and Su He Xiang Pill were the only prescription that were not required in the form of decoction and only prescribed in the severe stage. Traditional Chinese herbal medicines can consider as an important key in the management of new and emerging infectious disease.

Dr Catherine Poisson-Benatouil
Action of Artemisia annua on adaptive immunity in COVID-19 infections.
Concept note 1. Maison de l’Artemisia

Abstract

Antiviral herbal medicines have already been used in many epidemics, notably in the two previous coronavirus outbreaks - MERS-CoV in 2012, SARS-CoV in 2013 - or in seasonal epidemics caused by influenza or dengue viruses. In coronavirus infection (COVID-19), cellular adaptive immunity is primarily involved, in particular CD8 and CD4 lymphocytes that stimulate the B lymphocytes responsible for the production of antibodies targeting the coronavirus. In addition, there is a cytokine storm in patients infected with COVID-19 responsible for a major inflammatory response and their very severe progressive clinical state. The increase in interleukin-10 and TNF alpha reduces CD4 counts, causes functional exhaustion of immune cells and induces, at their site of action (liver, vascular endothelium), runaway production and action of inflammation proteins, causing the secondary aggravation of COVID-19 patients. Artemisia annua has a recognized antiviral activity (anti HSV1, Poliovirus, RSV, hepatitis C anti-virus, type 2 dengue virus, hantavirus, human cytomegalovirus) and antiHIV in vitro thanks to the flavonoids, quercetin and dicaffeoylquinic acids it contains. These molecules have been shown to inhibit the enzymaticactivity of CLPro (Chymotrypsin-like protease), an enzyme produced by SARS-CoV-2. The antiviral action of Artemisia annua, which is achieved by stimulating adaptive immunity, regulating the production of the pro-inflammatory cytokines prostaglandin E2 (PGE2), IL-6, IL-10, TNF alpha and increasing the genesis of CD4, CD8 and interferon gamma, involves many minerals and biomolecules : the properties of flavonoids, polyphenols, triterpenes, sterols, saponins, polysaccharides, artemisinin and its derivatives, the concentration of zinc, gallium and selenium in the plant play a role in the immune, antiviral, antioxidant and anti-inflammatory response. The plant is rich in Vitamins A and E, of which one, when supplemented, is known to reduce morbidity and mortality in viral infections, HIV among others, and the other is a powerful antioxidant. It is therefore the combination of these biomolecules and the intake of Artemisia annua in totum that could improve exhausted adaptive immunity and modulate the runaway inflammatory response during COVID-19 infection, as this plant has already demonstrated in other serious viral and parasitic infections.

Dr Catherine Poisson-Benatouil
Action de l’Artemisia annua sur l’immunité adaptative dans les infections COVID-19
Note de synthèse n° 1. Maison de l’Artemisia

Résumé

Les médicaments antiviraux à base de plantes ont été déjà utilisés lors de nombreuses épidémies, notamment lors les deux précédentes flambées de coronavirus - MERS-CoV en 2012, SRAS-CoV en 2013 - ou lors des épidémies saisonnières causées par les virus de la grippe ou de la dengue. Dans l’infection au Coronavirus (COVID-19), l’immunité adaptative cellulaire est essentiellement mise à contribution, en particulier les lymphocytes CD8 et les CD4 qui stimulent les lymphocytes B responsables de la production d’anticorps dirigés contre le Coronavirus. Par ailleurs, il existe un cyclone cytokinique chez les patients infectés par le COVID-19 responsable d’une réponse inflammatoire majeure et de leur état clinique évolutif très sévère. L’augmentation de l’Interleukine 10 et du TNF alpha réduit le nombre de CD4, provoque un épuisement fonctionnel des cellules de l’immunité et induit, sur leur site d’action (foie, endothélium vasculaire) un emballement de la production et de l’action des protéines de l’inflammation à l’origine de l’aggravation secondaire des patients COVID-19. L’Artemisia annua a une activité antivirale reconnue (anti HSV1, Poliovirus, VSR, antivirus de l’hépatite C, virus de la dengue de type 2, hanta virus, le cytomegalovirus humain) et anti VIH in vitro grâce aux Flavonoïdes, à la quercétine et aux acides dicaffeoyliquiniques qu’elle contient. Ces molécules ont montré qu’elles inhibent l’activité enzymatique de la chymotrypsine like protéase (CLPro). Cet enzyme est présent sur par le SARS-CoV2. L’action antivirale de l’Artemisia annua, qui s’effectue par la stimulation de l’immunité adaptative, la régulation de la production des cytokines pro-inflammatoires, Prostaglandine E2 (PGE2), IL-6, IL-10, TNF alpha et l’augmentation de la genèse des CD4 , des CD8 et de l’interféron gamma, fait intervenir de nombreux minéraux et biomolécules : les propriétés des flavonoïdes, polyphénols, triterpènes, des stérols, saponines, polysaccharides, artémisinine et ses dérivés, la concentration en zinc, gallium et sélénium dans la plante joue un rôle dans la réponse immunitaire, antivirale, antioxydante et anti-inflammatoire. La plante est in fine riche en Vitamine A et E dont l’une, en supplémentation, est reconnue pour réduire la morbidité et la mortalité dans les infections virales, VIH entre autres, et l’autre est un puissant antioxydant. C’est donc l’ensemble de ces biomolécules et la prise de l’Artemisia annua dans son totum qui pourrait améliorer l’immunité adaptative épuisée et moduler l’emballement de la réponse inflammatoire au cours de l’infection au COVID-19, comme cette plante en a déjà fait la preuve dans d’autres infections virales et parasitaires graves.

Dr Catherine Poisson-Benatouil
Transmembrane Serine Protease and Anti-Androgen Receptor Activity of Artemisia annua : another therapeutic option for COVID-19
Concept note 2. Maison de l’Artemisia, April 2020

Abstract

As early as 2011 for SARS-CoV-2003, it was noted that when a target cell expresses two receptors on its surface (such as type II pneumocytes), on the one hand the angiotensin converting enzyme type 2 (ACE2) receptor, a zinc metalloprotease, and on the other hand the transmembrane serine protease TMPRSS2 (TMPRSS2), it is more likely to be infected. Membrane expression of TMPRSS2 is known in the literature to be stimulated by androgen receptor (AR) expression on the cell surface. AR are expressed by the stimulation of androgens (A). For SARS-CoV-2, it has been shown that its cellular entry is blocked by a specific TMPRSS2 protease inhibitor. The first step for cell entry is therefore the AR activation of TMPRSS2 expression on the membrane surface of target cells that may possess both ACE2 and TMPRSS2 receptors. The initial priming of the S protein, spike protein, of the SARS-CoV-2 virus, is made on the expressed protease. Then, once priming is complete, the serine protease can cause cleavage of the ACE2 receptor present and thus increase the entry of the virus into the cell. Androgen expression of AR and therefore TMPRSS2 is known to occur in cells of the lung, prostate, gastrointestinal tract and upper airways and in certain cancerous prostate and lung tissues. This activation chain is particularly evident in tumor cells and metastatic cancers that are resistant to hormone therapy. Artemisinin, its derivatives and Artemisia annua have demonstrated their efficacy in inhibiting the growth of tumor and metastatic prostate cancer cells in vitro, in vivo and clinically in humans. Their action involves a decrease in androgen receptor expression and subsequently of TMPRSS2 involved in the diffusion of biochemical cellular messages stimulating the appearance of tumor and metastatic cells of the prostate. If artemisinin and its derivatives of Artemisia annua have this inhibitory capacity via AR on TMPRSS2 in prostate cancer, they could similarly have it on cells infected with SARS-CoV-2 and thus inhibit the initial priming of the viral S protein which is the first key to the stimulation of the ACE2 receptor and intracellular viral penetration.

Dr Catherine Poisson-Benatouil
Transmembrane Serine Protease and Anti-Androgen Receptor Activity of Artemisia annua : another therapeutic option for COVID-19
Note de synthèse n° 2. Maison de l’Artemisia, Avril 2020

Résumé

En 2011 déjà pour le SARSCOV 3, comme pour le virus Inflenzae, il était remarqué que lorsqu’une cellule cible exprimait à sa surface deux récepteurs (comme le pneumocyte de type 2), d’une part le récepteur de l’Enzyme de Conversion de l’Angiotensine de type 2 (ACE2) et d’autre part la Protéase Sérique transmembranaire TMPRSS2 (TMPRSS2), elle était davantage susceptible d’être infectée. L’expression membranaire de la TMPRSS2, est connue à ce jour, dans la littérature, pour être stimulée par l’expression des Récepteurs Androgéniques (RA) à la surface des cellules. Les RA s’expriment par la stimulation des androgènes (A). Pour le SARS COV2, il a été démontré que son entrée cellulaire était bloquée par un inhibiteur spécifique de la protéase TMPRSS2. La première étape à franchir, pour la pénétration cellulaire, est donc l’activation par les RA de l’expression de la TMPRSS2 à la surface membranaire des cellules cibles susceptibles de posséder les deux récepteurs, ACE2 et TMPRSS2. Sur la protéase exprimée se fait l’amorçage initiale de la protéine S, péplomère saillant du virus SARSCOV2. Ensuite, l’amorçage terminé, la protéase sérique peut provoquer le clivage du récepteur ACE2 présent et ainsi augmenter l’entrée du virus dans la cellule. L’expression par les androgènes des RA et par conséquence de la TMPRSS2 est connue dans les cellules du cancer de la prostate. Cette chaîne d’activation est décrite particulièrement dans les cellules tumorales et métastatiques ces cancers résistants à l’hormonothérapie. L’Artémisinine, ses dérivés, présents dans l’Artémisia Annua ont prouvé leur efficacité sur l’inhibition de la croissance des cellules tumorales et métastatiques du cancer de la prostate, in vitro, in vivo et chez l’homme cliniquement. Leur action passe par la diminution de l’expression des RA et subséquemment par celle de la TMPRSS2 impliquée dans la diffusion de messages cellulaires biochimiques stimulant l’apparition des cellules tumorales et métastatiques de la prostate. Si l’Artémisinine, ses dérivés de l’Artémisia Annua ont cette capacité inhibitrice via les RA sur la TPMRSS2 dans le cancer de la prostate, elles pourraient de même l’avoir sur les cellules infectées par le SARS COV2 et ainsi inhiber l’amorçage initiale de la protéine S virale première clé de la stimulation du récepteur ACE2 et de la pénétration virale intracellulaire.

Dr Catherine Poisson-Benatouil
Artemisia Annua, EMMPRIN, CYP A, PAK 1 et les métalloprotéases
Note de synthèse n° 3, Maison de l’Artemisia

Résumé

Au cours de la COVID 19, après la pénétration virale initiale, via la TMPRSS2 (protéase sérique) qui déclenche l’activation du récepteur ACE2 (récepteur de l’enzyme de conversion de l’angiotensine de type 2), le virus entre dans la cellule puis, au cours de sa maturation et pénétration intracytoplasmique, il exprime la Cyclophilline A (CyPA). Celle-ci déclenche l’expression extra-membranaire de la basigine ou CD147 ou EMMPRIN et son activation intracytoplasmique. La basigine agit de manière intra et extra-membranaire avec de nombreuses protéines. Une troisième molécule la Sérine /thréonine kinase (PAK1) dont l’expression est proportionnelle à celle de l’activation du récepteur ACE2 participe au processus pathologique viral.

L’activation de ces molécules qui agissent à l’extérieur et dans la cellule, est à l’origine d’un cyclone cytokinique et de l’amplification de la réaction inflammatoire de l’organisme via une activité chimiotactique intense entraînant l’activité et la circulation des leucocytes et des macrophages et enfin une induction des métalloprotéases (MMP) dont les inhibiteurs sont submergés dans cet état pathologique. À cela s’ajoute une sidération de la fonction lymphocytaire.Retour ligne automatique

Tous les signes cliniques qui résultent de cette réaction inflammatoire non contrôlée post invasive et de l’activation des métalloprotéases et des cytokines apparaissent chez le patient après quelques jours. En même temps, les récepteurs étant activés, la réplication virale se poursuit.

Artemisia annua peut enrayer ce cycle de réaction pathologique en agissant efficacement sur plusieurs cibles notamment le récepteur TMPRSS2, en inhibant son expression via les récepteurs androgéniques et donc la cascade d’activation de l’EMMPRIN et ses conséquences. Certaines biomolécules de l’Artemisia annua (artémisinine, et dérives, flavonoïdes, sesquiterpènes, polyphénols, quercétine) sont aussi des anti-inducteurs de métalloprotéases. Cette propriété a surtout été exploitée lors de traitement anticancéreux, pathologies où intervient aussi l’expression des métalloprotéases. Enfin l’artémisinine et ses dérivés sont des inhibiteurs naturels de la PAK1.

K. Abraham Peele, Chandrasai Potla Durthi, T. Srihansa, S. Krupanidhi, Vijaya Sai Ayyagari, D. John Babu, M. Indira A. Ranganadha Reddy, T.C. Venkateswarulu
Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2 : A computational study
Informatics in Medicine Unlocked Volume 19, 2020, 100345

Abstract

The aim of this study was to develop an appropriate anti-viral drug against the SARS-CoV-2 virus. An immediately qualifying strategy would be to use existing powerful drugs from various virus treatments. The strategy in virtual screening of antiviral databases for possible therapeutic effect would be to identify promising drug molecules, as there is currently no vaccine or treatment approved against COVID-19. Targeting the main protease (pdb id : 6LU7) is gaining importance in anti-CoV drug design. In this conceptual context, an attempt has been made to suggest an in silico computational relationship between US-FDA approved drugs, plant-derived natural drugs, and Coronavirus main protease (6LU7) protein. The evaluation of results was made based on Glide (Schrödinger) dock score. Out of 62 screened compounds, the best docking scores with the targets were found for compounds : lopinavir, amodiaquine, and theaflavin digallate (TFDG). Molecular dynamic (MD) simulation study was also performed for 20 ns to confirm the stability behaviour of the main protease and inhibitor complexes. The MD simulation study validated the stability of three compounds in the protein binding pocket as potent binders.

Cao R, Hu H, Li Y, Wang X, Xu M, Liu J, et al.
Anti-SARS-CoV-2 potential of artemisinins in vitro
ACS Infect Dis 2020 ; 6(9) : 2524–31.

Abstract

The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development.

Keywords : COVID-19 ; SARS-CoV-2 ; antiviral drug ; artemisinin ; drug repurposing.

Paulin M. Kapepula, Jimmy K. Kabengele, Micheline Kingombe, Françoise Van Bambeke, Paul M. Tulkens, Antoine Sadiki Kishabongo, Eric Decloedt, Adam Zumla, Simon Tiberi, Fatima Suleman, Lèon Tshilolo, Jean-Jacques Muyembe-Tam Fum, Alimuddin Zumla,† and Jean B. Nachega
Artemisia Spp. Derivatives for COVID-19 Treatment : Anecdotal Use, Political Hype, Treatment Potential, Challenges, and Road Map to Randomized Clinical Trials
American Journal of Tropical Medicine and Hygiene, 103(3), 2020, pp. 960–964 doi:10.4269/ajtmh.20-0820

Abstract

The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.

Sehailia M, Chemat S.
Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine : potential repurposing of artenimol for COVID-19.
J Biomol Struct Dyn 2020 ; 1–11. doi : 10.1080/07391102.2020.1796809.

Abstract

Medicinal herbs have proved along history to be a source of multiple cures. In this paper, we demonstrate how hydroxychloroquine can act as a good inhibitor of SARS-CoV-2 Spike protein receptor-binding-domain using molecular docking studies. We also unveil how hydroxychloroquine can interfere in the prevention of Lys353 in hACE2 from interacting with the corresponding binding hotspot present on the Spike protein. Further screening of artemisinin & derived compounds produced better Vina docking score than hydroxychloroquine (-7.1 kcal mol−1 for artelinic acid vs. −5.5 kcal mol−1 for hydroxychloroquine). Artesunate, artemisinin and artenimol, showed two mode of interactions with Lys353 and Lys31 binding hotspots of the Spike protein. Molecular dynamics analysis confirmed that the formed complexes are able to interact and remain stable in the active site of their respective targets. Given that these molecules are effective antivirals with excellent safety track records in humans against various ailment, we recommend their potential repurposing for the treatment of SARS-CoV-2 patients after successful clinical studies. In addition, an extraction protocol for artemisinin from Artemisia annua L. is proposed in order to cope with the potential urgent global demand. Communicated by Ramaswamy H. Sarma Keywords : SARS-CoV-2, COVID-19, spike protein, hACE2, antiviral, hydroxychloroquine, artemisinin

Keywords : SARS-CoV-2, COVID-19, spike protein, hACE2, antiviral, hydroxychloroquine, artemisinin

Alsaffar D, Yaseen A, Jabal G.
[In silico molecular docking studies of medicinal Arabic plant-based bioactive compounds as a promising drug candidate against COVID-19.]
Int J Innov Sci Res Technol 2020 ; 5(5) : 876–96

Ruolan Dong, Xinyu Xiong, Guang Chen
Discuss about the application of Artemisia annua prescriptions in the treatment of COVID-19
TMR Modern Herbal Medicine, Aug 2020, Vol.3, no.3, 1

Abstract

The applications of traditional Chinese medicine (TCM) have been playing an important role in treating the epidemics of Coronavirus Disease 2019 (COVID-19), which is now prevalent all over the world. Exploring the mechanisms of TCM compound prescriptions might be difficult though, pharmacological studies on elucidating the effective components of TCM could serve as the experimental basis in the application of TCM compound prescription in treating COVID-19. As the critical active ingredients of Qinghao (Artemisia annua), artemisinin was initially used as antimalaria drug. Artemisia annua prescriptions take significant effect against pneumonia. Sharing similarities in pharmacology with artemisinin, chloroquine has been confirmed effective in inhibiting Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) both in vitro and practically. In this context, we discussed the application of Artemisia annua prescriptions against COVID-19 along with the antiviral effect of chloroquine.

Keywords : COVID-19, Chloroquine, Artemisinin, Artemisia annua

Excerpt :

« Based on the effect of clearing dampness and heat, Artemisia annua prescriptions receive good results in treating the Novel Coronavirus Pneumonia patients. Exploring the possible mechanism of Artemisia annua prescriptions in treating new coronavirus pneumonia is conducive to the popularization of this prescription and has important clinical value. This review will discuss the possible mechanism that Artemisia annua prescriptions treat new coronavirus pneumonia by comparing the similar protective effect of artemisinin and chloroquine in epidemic diseases.
[...]
Based on the antiviral and anti-inflammatory effects of artemisinin and its derivatives, Artemisia annua prescriptions have great value to dig into and are promising to be used in more infectious diseases. But more in vitro experiments need to be carried out to provide more evidence, such as the influence of Artemisia or Artemisia annua prescriptions on inflammatory factors expression and lung injury in acute infectious diseases. »

Andrea D. Fuzimoto, Ciro Isidoro
The antiviral and the coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - Additional weapons in the fight against the COVID-19 pandemic ?
Journal of Traditional and Complementary Medicine 10 (2020) 405e419

Abstract

Introduction : As of March 11th, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Articles published after the SARS-CoV-1 (2002) epidemic suggest that the use of an herbaldrug integrative medical approach could have contributed to a lower fatality rate and a more rapid response in controlling the outbreak. Methods : Pubmed was searched for articles that investigated the antiviral properties and mechanisms of action of herbs or natural compounds against the SARS-coronavirus (CoV).

Results : Forty-three relevant papers were located. A general count rendered 450þ herbs and natural compounds with antiviral properties against the SARS-CoV and related viruses. From the 43 articles, thirty-one uncovered the mechanisms of action of the natural substances able to oppose the coronavirus. Discussion : A series of herbs and natural compounds demonstrated moderate to strong antiviral activity. Research on many herbs-natural compounds also showed potent and significant inhibition of CoV-host protein pathways responsible for different phases of viral replication specifically targeting 3CLPRO, PLPRO, RdRp, helicase protein, S protein, N protein, 3a protein, Cathepsin L, Nsp1, Nsp3c, and ORF7a, and the S protein/ACE-2 interaction. Conclusion : The herbs-natural compounds with antiviral activity and that caused inhibition/blockade of the CoV-host protein pathways are potential therapeutic candidates. The homology between the SARSCoV- 1 and SARS-CoV-2 is around 80%. Thus, effective herbs-compounds for the former would likely be beneficial for the latter also depending on target protein similarities between the viruses. Here we provide the mechanistic bases supporting an integrative approach that includes natural compounds to fight coronavirus infections.

2021

Juwairiah Remali and Wan Mohd Aizat
A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection
Frontiers in Pharmacology, published : 11 January 2021, 11:589044. doi : 10.3389/fphar.2020.589044.

Abstract :

The rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19 as treatment is mostly directed to only relieving the symptoms. Retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative including for the treatment of various viral illnesses. However, a comprehensive description using various medicinal plants in treating coronavirus infection has not to date been described adequately, especially their modes of action. Most other reports and reviews have also only focused on selected ethnobotanical herbs such as Traditional Chinese Medicine, yet more plants can be considered to enrich the source of the anti-viral compounds. In this review, we have screened and identified potential herbal medicinal plants as anticoronavirus medication across major literature databases without being limited to any regions or ethnobotanic criteria. As such we have successfully gathered experimentally validated in vivo, in vitro, or in silico findings of more than 30 plants in which these plant extracts or their related compounds, such as those of Artemisia annua L., Houttuynia cordata Thunb., and Sambucus formosana Nakai, are described through their respective modes of action against specific mechanisms or pathways during the viral infection. This includes inhibition of viral attachment and penetration, inhibition of viral RNA and protein synthesis, inhibition of viral key proteins such as 3-chymotrypsin-like cysteine protease (3CLpro) and papain-like protease 2 (PLpro), as well as other mechanisms including inhibition of the viral release and enhanced host immunity. We hope this compilation will help researchers and clinicians to identify the source of appropriate anti-viral drugs from plants in combating COVID-19 and, ultimately, save millions of affected human lives.

Keywords : COVID-19, drug, herb, SARS, Traditional Chinese medicine (TCM), medicinal plant, natural products, viral infection

Chuanxiong Nie, Jakob Trimpert, Sooyeon Moon, Rainer Haag, Kerry Gilmore, Benedikt B. Kaufer, and Peter H. Seeberger
In vitro efficacy of Artemisia extracts against SARS-CoV-2
bioRxiv preprint doi : https://doi.org/10.1101/2021.02.14.431122 ; this version posted February 15, 2021.

Abstract :

Traditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in efforts to prevent and fight COVID-19 infections. We sought to study the ability of different A. annua and A. afra extracts and the Covid-Organics drink produced in Madagascar to inhibit SARSCoV-2 and feline coronavirus (FCoV) replication in vitro. Several extracts as well as CovidOrganics inhibit SARS-CoV-2 and FCoV replication at concentrations that did not affect cell viability. It remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral replication following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment in patients.

Keywords : Artemisia annua ; Artesunate ; Antivirals ; COVID-19 ; Covid-Organics ; Feline coronavirus (FCoV) ; SARS-CoV-2.

Kshirsagar, S.G. ; Rao, R.V.
Antiviral and Immunomodulation Effects of Artemisia.
Medicina 2021, 57, 217. https://doi.org/10.3390/ medicina57030217

Abstract :

Background and Objectives : Artemisia is one of the most widely distributed genera of the family Asteraceae with more than 500 diverse species growing mainly in the temperate zones of Europe, Asia and North America. The plant is used in Chinese and Ayurvedic systems of medicine for its antiviral, antifungal, antimicrobial, insecticidal, hepatoprotective and neuroprotective properties. Research based studies point to Artemisia’s role in addressing an entire gamut of physiological imbalances through a unique combination of pharmacological actions. Terpenoids, flavonoids, coumarins, caffeoylquinic acids, sterols and acetylenes are some of the major phytochemicals of the genus. Notable among the phytochemicals is artemisinin and its derivatives (ARTs) that represent a new class of recommended drugs due to the emergence of bacteria and parasites that are resistant to quinoline drugs. This manuscript aims to systematically review recent studies that have investigated artemisinin and its derivatives not only for their potent antiviral actions but also their utility against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Materials and Methods : PubMed Central, Scopus and Google scholar databases of published articles were collected and abstracts were reviewed for relevance to the subject matter.

Conclusions : The unprecedented impact that artemisinin had on public health and drug discovery research led the Nobel Committee to award the Nobel Prize in Physiology or Medicine in 2015 to the discoverers of artemisinin. Thus, it is clear that Artemisia’s importance in indigenous medicinal systems and drug discovery systems holds great potential for further investigation into its biological activities, especially its role in viral infection and inflammation.

Joshua Iseoluwa Orege, Sherif Babatunde Adeyemi, Bashir Bolaji Tiamiyu, Toluwanimi Oluwadara Akinyemi, Yusuf Ajibola Ibrahim & Odunola Blessing Orege
Artemisia and Artemisia-based products for COVID-19 management : current state and future perspective.
Advances in Traditional Medicine. https://doi.org/10.1007/s13596-021-00576-5
Published : 05 May 2021

Abstract

The search for a potent anti-coronavirus therapy for severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) remains an overwhelming task since the outbreak of COVID-19. It is more evident that most of the existing antiviral and immune-boosting drugs are non-promising and ineffective for the treatment of coronavirus infected patients while the safety of a few drugs/vaccines that have demonstrated high potential remains unclear. With daily records of confirmed infectious cases across the world, it is crucial to emphasize the need for repurposed therapies with a validated ethnomedicinal base focused on well-known active medicines with traceable biochemical, pharmacological and safety profiles for viral infection management. In the present study, recent literature on Artemisia and Artemisia-based products for the management of COVID-19 are reviewed. Artemisia-based products have demonstrated a broad spectrum of biological ability including antiviral properties. Besides its antiviral activity, Artemisia annua have shown to contain appreciable amounts of minerals such as zinc, gallium and selenium among others.

Sourav Das, Sharat Sarmah, Sona Lyndem, and Atanu Singha Roy
An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study
J Biomol Struct Dyn. 2020 : 1–11.

Abstract

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB : 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions. Communicated by Ramaswamy H. Sarma

Keywords : SARS-CoV-2 Mpro, molecular docking, natural products, anti-virals, anti-fungals

Andréa D. Fuzimoto
An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment
Journal of Integrative Medicine, 2021 Jul 22, doi : 10.1016/j.joim.2021.07.003

Abstract

An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment Andréa D. Fuzimoto Holistic Sync—Holistic Integrative Medicine, USA/Brazil ABSTRACT Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised : do A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. PubMed/MEDLINE, Scopus, and Google Scholar were searched for peerreviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that studied the herb’s role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins, including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nsp3, nsp10, nsp14, nsp15, and GRP78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, and internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua’s biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing of A. annua compounds are discussed. The combination of A. annua’s biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection.

Tariq Khan, Mubarak Ali Khan, Zia-ur-Rehman Mashwani, Nazif Ullah, Akhtar Nadhman
Therapeutic potential of medicinal plants against COVID-19 : The role of antiviral medicinal metabolites
Biocatalysis and Agricultural Biotechnology 31 (2021) 101890

Abstract :

There are numerous trials underway to find treatment for the COVID-19 through testing vaccines as well as existing drugs. Apart from the many synthetic chemical compounds, plant-based compounds could provide an array of \suitable candidates for testing against the virus. Studies have confirmed the role of many plants against respiratory viruses when employed either as crude extracts or their active ingredients in pure form. The purpose of this review article is to highlight the importance of phytomedicine against COVID-19. The main aim is to review the mechanistic aspects of most important phytochemical compounds that have showed potential against coronaviruses. Glycyrrhizin from the roots of Glycyrrhiza glabra has shown promising potential against the previously epidemic coronavirus, SARS-CoV. Other important plants such as Artemisia annua, Isatis indigotica, Lindera aggregate, Pelargonium sidoides, and Glychirrhiza spp. have been employed against SARS-CoV. Active ingredients (e.g. emodin, reserpine, aescin, myricetin, scutellarin, apigenin, luteolin, and betulonic acid) have shown promising results against the coronaviruses. Phytochemicals have demonstrated activity against the coronaviruses through mechanisms such as viral entry inhibition, inhibition of replication enzymes and virus release blockage. However, compared to synthetic drugs, phytomedicine are mechanistically less understood and should be properly evaluated before application. Nonetheless, phytochemicals reduce the tedious job of drug discovery and provide a less time-consuming alternative for drug testing. Therefore, along with other drugs currently tested against COVID-19, plant-based drugs should be included for speedy development of COVID-19 treatment.

Abdirahman ELMI, Ahmed Said MOHAMED, Nazia SIDDIQUI, Syad AL JAWAD, Moustapha NOUR, Idriss MIGANEH and Saleem JAVED
Identification of potential inhibitors of SARS CoV 2 from Artemisia annua compounds by in silico evaluation and their density functional theory (DFT)
Journal of Drug Delivery & Therapeutics. 2021 ; 11(1-s):71-82

Abstract :

The genus Artemisia has recognized medicinal value and its use by humans Dates back to centuries ago. With the appearance of the new coronavirus, end of 2019, several countries have recommended the use of herbal teas consisting mainly of Artemisia. The individual analysis of the constituents of this species is crucial to characterize and optimize its antiSARS-Cov-2 action. We evaluated by molecular docking the inhibitory action of major compounds of the Artemisia genus (Artemisinin, Arteannuin B, Alpha Thujone, P-Hydroxyacetophenone, Fisetin, Cirsimaritin, Capillin, β-Sitosterol, and Quercetin) against three targets namely SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor binding domain (RBD) and human furin protease (HF protease). The two flavonols, quercetin and fisetin, have the best binding energies with the three targets. Quercetin/Fisetin possesses binding energy of -7.17/-6.9, -6.3/-6.15 and – 5.98/- 5.49 kcal/mol with MP, RBD and HF protease respectively. Their physicochemical properties meet the requirements of an oral active principle and are not toxic according to predictive simulations. Thereby DFT calculation has been used to analyze the electronic and geometric characteristics of these two compounds. The gap energies were also deduced for the stable structure and their reactivity. The abundance of Quercetin in different plants may be another advantage in the use of this bio-compound in the treatment of coronavirus.

Keywords : Artemisia annua, DFT, Docking Molecular, SARS-Cov-2, Quercetin and Fisetin

Chuanxiong Nie, Jakob Trimpert, Sooyeon Moon, Rainer Haag, Kerry Gilmore, Benedikt B. Kaufer and Peter H. Seeberger
SHORT REPORT. In vitro efcacy of Artemisia extracts against SARS-CoV-2
Virol J (2021) 18:182

Abstract

Background : Traditional medicines based on herbal extracts have been proposed as afordable treatments for patients sufering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in eforts to prevent SARS-CoV-2 infection and fght COVID-19.

Methods : The plant extracts and Covid-Organics drink produced in Madagascar were tested for plaque reduction using both feline coronavirus and SARS-CoV-2 in vitro. Their cytotoxicities were also investigated.

Results : Several extracts as well as Covid-Organics inhibited SARS-CoV-2 and FCoV infection at concentrations that did not afect cell viability.

Conclusions : Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.

Keywords : Artemisia annua, Artemisia afra, Antivirals, COVID-19, Covid-organics, Feline coronavirus (FCoV), SARSCoV-2

Naira, M.S., Huanga, Y., Fidock, D.A., Polyakd, S.J., Wagonerd, J., Towlere, M.J., Weathers, P.J. Aaron Diamond
Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants
AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Abstract

SARS-CoV-2 (Covid-19) globally has infected and killed millions of people. Besides remdesivir, there are no approved small molecule-based therapeutics. Here we show that extracts of the medicinal plant, Artemisia annua L., which produces the antimalarial drug artemisinin, prevents SARS-CoV-2 replication in vitro. We measured antiviral activity of dried leaf extracts of seven cultivars of A. annua sourced from four continents. Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC 50 values of 0.1-8.7 μM, 0.01-0.14 μg, and 23.4-57.4 μg, respectively. One sample was >12 years old, but still active. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts and antiviral efficacy was inversely correlated to artemisinin and total flavonoid contents. Artemisinin alone showed an estimated IC 50 of about 70 μM, and antimalarial artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC 50 = 5.8 μM. The extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude of the antiviral IC 90 values. Results suggest the active component in the extracts is likely something besides artemisinin or is a combination of components acting synergistically to block post-entry viral infection. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.

Mis en ligne par La vie re-belle
 25/05/2020
 https://lavierebelle.org/artemisia-annua-et-coronavirus

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Bibliographie : Potentiel antiviral d’Artemisia annua L. et Artemisia afra Jacq.

Ce dossier regroupe les publications concernant le potentiel antiviral d’Artemisia annua L. et Artemisia afra Jacq.

Les articles 1

Cet article présente et permet l’accès aux recherches publiées relatives aux propriétés antibactériennes, antivirales, immunomodulatrices et immunoprotectrices (...)
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