Bibliography: Antiviral potential of Artemisia annua L.

Artemisia annua et traitement des Coronavirus

This article presents and provides access to published research on the antiviral and immunomodulatory and immunoprotective properties of Artemisia annua and its active ingredients.The studies and their abstracts are presented according to the chronology of their publication since the first publication in 2004 of a WHO study mentioning the use of Artemisia annua in the treatment of SARS-CoV2.

Artemisia et Coronavirus

Bibliography: Antiviral potential of Artemisia annua L.

Artemisia annua et traitement des Coronavirus


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. [...] s. 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


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 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.


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


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.


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)


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.


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


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.

Vincent C. C. Cheng, Susanna K. P. Lau, Patrick C. Y. Woo, et Kwok Yung Yuen
Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection
Clinical Microbiology Reviews, Oct. 2007, p. 660-694 Vol. 20, No. 4, American Society for Microbiology.

Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection

No Abstract


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


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


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.

Abstract in English but full text in Chinese not available


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.


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


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

James T. Mukinda; James A. Syce; David Fisher; Mervin Meyer
Effect of the plant matrix on the uptake of luteolin derivatives-containing Artemisia afra aqueous-extract in Caco-2 cells
Journal of Ethnopharmacology. 2010 Aug 9; 130(3): 439-49.

Effect of the plant matrix on the uptake of luteolin derivatives-containing Artemisia afra aqueous-extract in Caco-2 cells


Aim of the study: Luteolin is a major flavonoid constituent and a primary candidate that might contribute to the claimed in vivo protective effects of Artemisia afra (Jacq. Ex. Willd). However, an exhaustive search yielded no literature evidence on the absorption, metabolism and fate of this flavonoid from the traditional plant preparation. The purpose of this study was to investigate the effect of the plant matrix on the uptake of luteolin derivatives from Artemisia afra aqueous extract in human intestinal epithelial Caco-2 cells.

Materials and methods: Cell monolayers were incubated with 5, 10 and 20?g/ml doses of luteolin aglycone, luteolin-7-0-glucoside, un-hydrolyzed or acid-hydrolyzed Artemisia afra extracts, and samples of 150?l each were collected from both apical and basolateral sides of cells at 30, 60 and 120min for HPLC and LC–MS analyses.

Results: After 1-h exposure, the uptake of luteolin aglycone and luteolin-7-0-glucoside from the unhydrolyzed and acid-hydrolyzed extracts was significantly faster and quantitatively higher (i.e. >77% vs. < 25% of the initial doses over the first 30min, p < 0.05) than that from non-plant solutions. Apical to basolateral permeability coefficients for luteolin and its-7-0-glucoside in the extracts were 1.6- to 2-fold higher than that for the non-plant solutions. Glucuronidation was an important pathway of metabolismfor luteolin in both non-plant and plant extract forms.

Conclusions: Luteolin in Artemisia afra aqueous extract, regardless of its form (i.e. whether aglycone and 7-0-glucoside), is taken up better and more efficiently metabolized than the aglycone and 7-0-glucoside forms administered as pure solutions in Caco-2 cells. Flavonoid actives from Artemisia afra plant extracts and especially traditionally prepared dosage forms may thus have better bioavailability, and consequently greater in vivo potency, than that predicted from studies done using the pure solutions

Keywords: Artemisia afra, Flavonoid, Luteolin, Glucosides, Transepithelial, transport, Caco-2 cells, Bioavailability


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


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

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


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

Gayathri V. Patil, Sujata K. Dass and Ramesh Chandra
Artemisia afra and Modern Diseases
Journal of Pharmacogenomics & Pharmacoproteomics 2011, 2:3

Artemisia afra and Modern Diseases


Herb Artemisia afra has recently attracted worldwide attention of researchers for its possible use in the modern diseases like diabetes, cardiovascular diseases, cancer, respiratory diseases etc. This review is exhaustive and systematic organization of the available literature on Artemisia afra (A. afra) from January 1922 to July 2011. The literature survey presents the number of publications with respect to time. Patents are briefly described; the traditional uses are classified and summarized. Some emphasis is given to the data and projections of modern diseases and the ongoing research in this area in the context of title of this review. The pharmacognostic aspects, chemical constituents and factors affecting it, the activity, analysis & quality control, pharmaceutical dosage form etc. is dealt in this review.

Keywords: Artemisia afra; Patents; Traditional uses; Chemical constituents; Activity; Toxicity; Dosage form


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


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.


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


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.

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


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

Pierre Lutgen
Luteolin in the Artemisia family, 16 mars 2013

Luteolin in the artemisia family

No abstract


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


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


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


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


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


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


Pierre Lutgen
Tannins in Artemisia: hidden treasure for prophylaxis
Text published on the web site Malaria world, October 9, 2016

Tannins in Artemisia: hidden treasure for prophylaxis

No abstract


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


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 PTEN/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


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


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


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.


Action antivirale (de l’artemisinine)

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

Redeploying plant defences

Journal Editorial

No abstract

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


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.

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)


4.2.2 Mild cases 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. 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 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


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 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.


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.


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.

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, L´ eon Tshilolo, Jean-Jacques Muyembe-Tam Fum, Alimuddin Zumla,† and Jean B. Nachega
Perspective Piece
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


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.

M. Hesam Shahrajabian and Wenli Sun
Exploring Artemisia annua L., artemisinin and its derivatives, from traditional Chinese wonder medicinal science
Notulae Botanicae Horti Agrobotanici Cluj-Napoca 48(4):1719-1741


Artemisia annua L. (Chinese wormwood herb, Asteraceae) synthesizes artemisinin, which is known as qinghaosu, considers as a unique sesquiterpene endoperoxide lactone. In traditional Chinese medicine, it has been used for the treatment of fevers and haemorrhoides. More researches on Artemisia annua L. and its derivatives, especially artemisinin and other metabolites will help to increase the knowledge and value of A. annua and its constituents. Phenolics from Artemisia annua consists of coumarins, flavones, flavonols, phenolic acids, and miscellaneous. Artemisinin has attracted much attention from scientists due to its potent antimalarial properties as secondary metabolites. Moreover, more attentions are focusing on the roles of artemisinin and its derivatives in treating obesity and metabolic diseases. They also have anti-bacterial, antiinflammatory, anti-tumor, anti-protozoa, anti-helminthic, anti-fungal, anti-angiogenic and antiproliferation properties. The most important derivatives of Artemisia annua L. are arteether, artemether, artemiside, artemisinin, artemisone, artesunate, and dihydroartemisinin. Artemisinin also use against some cancers such as liver cancer, brain glioma, leukemia, nasopharyngeal cancer, gallbladder cancer, gastric cancer, cervical cancer, lung cancer, breast cancer and colon cancer. This important gift from ancient Chinese traditional medicine can guarantee health of people all around the world. Further researches should be done on the new advances and development of artemisinin and its derivatives as potential natural medicine in the global fight against so many diseases, malaria included.

Keywords: artemisia; artemisinin; cancer; Chinese medicine; malaria

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.


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


« 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. »


Juwairiah Remali and Wan Mohd Aizat
A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection
Fontiers in Pharmacology, published: 11 January 2021, 11:589044. doi: 10.3389/fphar.2020.589044. eCollection 2020.

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

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

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.

Published online by La vie re-belle


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Bibliography: Antiviral potential of Artemisia annua L. and Artemisia afra Jacq.

This file contains publications concerning the antiviral potential of Artemisia annua L. and Artemisia afra Jacq.

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