This article, regularly updated, presents and provides access to published research related to the antiviral, 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. The first studies on the antiviral and immunostimulant properties of Artemisia annua were published in China in the early 1980s. The first publication of a study mentioning the use of Artemisia annua in the treatment of SARS-CoV2 was in 2004. The number of publications concerning the potential of Artemisia annua and its active compounds to neutralize Coronaviruses has multiplied since the beginning of the COVID-19 pandemic.
1981
Qian RS, Li ZL, Yu JL, et al.
Immunological and anti-viral actions of artemisinin
J Tradit Chin Med 1981; 22 (5): 462 – 6 .
Qian RS, Li ZL, Yu JL, Ma DJ.
The immunologic and antiviral effect of qinghaosu.
J Tradit Chin Med. 1982 Dec;2(4):271-6. PMID: 6765722.
In the early 1980s the Journal of Traditional Chinese Medicine, funded by the Beijing University of Chinese Medicine and supervised by the Chinese Ministry of Education, published a series of articles that are, to our knowledge, the first studies of the immunostimulant and antiviral properties of artemisinin. Unfortunately neither the texts nor the abstracts of these studies are available.
1984
Shen M, Ge HL, He YX, Song QL, Zhang HZ.
Immunosuppressive action of Qinghaosu
Sci Sin B. 1984 Apr;27(4):398-406. PMID: 6379875
Full text non available
Abstract
Qinghaosu, isolated and purified from the Chinese herb, Artemisia annua Linn, and identified as a sesquiterpene with a peroxide bridge and lactone structure, is a highly potent and non-toxic new antimalaria drug. This paper reports the immunosuppressive action of its water soluble derivative (hemisuccinate NA, QHS). The remarkable suppression by QHS of the in vitro 3HTdR incorporation by mitogen-stimulated mouse spleen cells and human peripheral lymphocytes, as well as the spontaneous incorporation by mouse thymocytes and blood cells from some leukemia patients is presented and its characteristics are described. The in vivo effect as shown by quantitative PFC is studied and the difference between the present in vitro and in vivo effects is investigated. The possible mechanism of inhibition and discrepancy in effects are discussed.
1991
Abid Ali Khan MM, Jain DC, Bhakuni RS et al (1991)
Occurrence of some antiviral sterols in Artemisia annua
Plant Sci 75:161–165
- Occurrence of some antiviral sterols in Artemisia annua
Abstract
Out of the twenty one medicinal plants evaluated for their virus inhibitory activity against tobamoviruses on their test hosts reacting hypersensitively, extracts of Lawsonia alba, Artemisia annua and Cornus capitata showed high virus inhibitory activity. The virus inhibitory agent (s) occurring in A. annus plant was isolated by conventional methods and identified as sterols. The sterols were characterized by spectral methods as sitosterol and stigmaterol.
Key words: tobamoviruses: Artemisia annua; virus inhibitory agent(s): /3-sitosterol; stigmasterol
Sun XZ.
Experimental study on the immunosuppressive effects of qinghaosu and its derivative
Zhong Xi Yi Jie He Za Zhi. 1991 Jan;11(1):37-8, 6. Chinese. PMID: 2054892.Article written in Chinese
English abstract published:
In this report the researches studied the immunosuppressive effects of Qinghaosu (QHS) and its derivative (DQHS). The results indicated that after 7-day successive administration i.p of QHS and DQHS at the dosage of 25-100 mg/kg, the amounts of anti-SRBC IgM PFC and IgG PFC in the murine spleen were decreased significantly (P less than 0.01). At the dosage of 100 mg/kg the QHS and DQHS were able to inhibit the DTH induced with BSA and the proliferative responses of murine spleen cells to Con A and LPS. These results suggested the suppressive effects of QHS and DQHS on both humoral and cellular immunities of mice. Interleukin-2 (IL-2) is an important mediate in the immune response and plays a critical role in the activation and differentiation of T and B lymphocytes. The results in this report showed a significant suppression of IL-2 production of murine spleen cells after 7-day administration i. p of QHS and DQHS, which suggested that the inhibition of IL-2 production could be the important one of the mechanisms of the immunosuppressive effects of QHS and DQHS.
1994
Mankil Jung; Raymond F. Schinazi (1994)
Synthesis and in vitro anti-human immunodeficiency virus activity of artemisinin (qinghaosu)-related trioxanes
Bioorganic & Medicinal Chemistry Letters, volume 4, issue 7
Abstract
A series of artemisinin (qinghaosu)-related trioxanes has been prepared and assayed in vitro for anti-HIV activity. One of these compounds, 12-n-butyldeoxoartemisinin shows a good antiviral activity against HIV-1.
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
Artemisia annua was one of the therapeutic responses that were used in China to counter the deleterious effects of the severe acute respiratory syndrome or SARS-CoV that appeared in November 2002 in Guangdong province. The WHO-sponsored study published in 20041 compared several types of treatments that were then used to control the outbreak. The results showed that the administration of decoctions including Artemisia annua in addition to conventional treatments was often effective in alleviating symptoms.
Thereport is not preceded by an abstract
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): 307–11Article in Chinese
English abstract published:->http://en.cnki.com.cn/Article_en/CJFDTotal-TRCW200404008.htm]
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.
Suzanne J F Kaptein, Thomas Efferth, Martina Leis, Sabine Rechter, Sabrina Auerochs, Martina Kalmer, Cathrien A Bruggeman, Cornelis Vink, Thomas Stamminger, Manfred Marschall
The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo
Antiviral Research Volume 69, Issue 2, February 2006, Pages 60-69
Abstract
Treatment of human cytomegalovirus (HCMV) infections with any of the currently available antiviral agents is frequently associated with the occurrence of severe complications, seriously threatening the successful outcome of treatment. Therefore, the development of novel antiviral strategies is a challenging goal of current investigations. Previously, we reported that artesunate (ART) is an effective, non-cytotoxic inhibitor of HCMV in vitro. Here, we demonstrate that the efficacy of the antiviral effect of ART is augmented by co-treatment of HCMV-infected fibroblasts with ferrous iron, i.e. Ferrosanol, and/or the iron transfer-mediating molecule holo-transferrin. This could alleviate the HCMV-induced modulation of cell surface expression of adhesion molecule Thy-1, suggesting that ART might be able to prevent pro-inflammatory effects of infection. The iron-enhanced, antiviral effect of ART could also be demonstrated in cultured cells infected with rat cytomegalovirus. Experiments using the RCMV/rat model showed that both the viral DNA load and virus titers in the salivary glands from infected rats were significantly reduced upon treatment with ART. Furthermore, an additive antiviral effect for ART together with each one of conventional anti-HCMV drugs, i.e. ganciclovir, cidofovir or foscarnet, was detected in HCMV-infected fibroblasts. These findings might open new perspectives regarding the use of ART in clinical trials.
2007
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.
Abstract
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
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.
2011
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
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
Ho WE, Peh HY, Chan TK, Wong WS.
Artemisinins: pharmacological actions beyond anti-malarial
Pharmacol Ther. 2014 Apr;142(1):126-39. doi: 10.1016/j.pharmthera.2013.12.001. Epub 2013 Dec 6. PMID: 24316259.
Abstract
Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from Artemisia annua L. The anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the Plasmodium species. With its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. Artemisinins have been reported to possess robust inhibitory effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis. Artemisinins have been evaluated in animal models of autoimmune diseases, allergic disorders and septic inflammation. The anti-inflammatory effects of artemisinins have been attributed to the inhibition of Toll-like receptors, Syk tyrosine kinase, phospholipase Cγ, PI3K/Akt, MAPK, STAT-1/3/5, NF-κB, Sp1 and Nrf2/ARE signaling pathways. This review provides a comprehensive update on non-malarial use of artemisinins, modes of action of artemisinins in different disease conditions, and drug development of artemisinins beyond anti-malarial. With the concerted efforts in the novel synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is likely that artemisinin drugs will become a major armamentarium combating a variety of human diseases beyond malaria.
Keywords: Allergy; Artesunate; Autoimmune disorder; Cancer; Dihydroartemisinin; Infection.2015
Shi C, Li H (2015)
Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives
Mediat Inflamm 2015:435713
Abstract
Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.
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 μM for CCRF-CEM and IC 50 up to 0.20 μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC 50 1.61 μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer 6 is the most efficient hybrid (IC 50 0.04 μM) outperforming ganciclovir (IC 50 2.6 μM), dihydroartemisinin (IC 50 >10 μM) and artesunic acid (IC 50 3.8 μM).
Keywords: Artemisinin-derived hybrids, Artemisinin-derived dimers, Artemisinin-derived trimers, Antimalarial activity, Anticancer activity, Antiviral activity
L D Bao, X H Ren, R L Ma, Y Wang, H W Yuan, H J Lv
Efficacy of Artemisia annua polysaccharides as an adjuvant to hepatitis C vaccination
Genet Mol Res. 2015 May 11;14(2):4957-65. doi: 10.4238/2015.May.11.29. PMID: 25966271.
Abstract
The traditional Chinese medicine Artemisia annua can prevent and treat hepatitis following an unclear mechanism. The aim of this study was to evaluate the effects of A. annua polysaccharides (AAP) on hepatitis C virus (HCV). A pcDNA3.1/NS3 expression vector was constructed. Ninety female BALB/c mice were randomly divided into six groups: high-dose AAP (1 mg/mL) + HCV/NS3 plasmid; middle-dose AAP (0.5 mg/mL) + HCV/NS3 plasmid; low-dose AAP (0.1 mg/mL) + HCV/NS3 plasmid; HCV/NS3 plasmid; high-dose AAP (1 mg/mL); normal saline control (N = 15). Except the control group and the high-dose AAP group, other groups were inoculated with 50 μg pcDNA3.1-HCV/NS3 plasmid. Serum antigenic-specific antibody was detected after the last immunization, and the levels of secreted IFN-γ and IL-4 were measured. pcDNA3.1/NS3 plasmid was successfully constructed, and the extracted product contained HCV/NS3 sequence. Compared with single inoculation with HCV/NS3 DNA vaccine, the specific antibody levels induced by middle-dose AAP plus HCV/NS3 DNA vaccine were significantly different in weeks 1, 3 and 5 (P < 0.05). However, there were no significant differences in the antibody levels induced by high-dose and low-dose AAP as adjuvant compared with those of single inoculation with DNA vaccine (P > 0.05). The level of serum IFN-γ secretion was significantly higher than that of IL-4 secretion. Compared with the single HCV/NS3 DNA vaccine group, AAP plus HCV/NS3 DNA vaccine groups had significant increased IFN-γ levels (P < 0.05), but the IL-4 levels were not significantly different among these groups (P > 0.05). AAP, as the adjuvant of HCV/NS3 DNA vaccine, can widely regulate the humoral immunity and cellular immune function of normal and cyclophosphamide-induced immunocompromised mice. AAP can promote IFN-γ secretion probably by inducing Th1-type cellular immune response.
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
2016
Wenbo Yao, Feng Wang, Hui Wang
Immunomodulation of artemisinin and its derivatives
Sci. Bull. (2016) 61(18):1399–1406
Abstract
In the 1970s, artemisinin (“qinghaosu” in Chinese), a sesquiterpene lactone with an unusual peroxide bridge, was isolated from Artemisia annua L. It showed promising antimalarial activity, particularly by eliminating parasites resistant to chloroquine. For more than 30 years, artemisinin has contributed to worldwide health as a new type of antimalarial drug. Artemisinin and its analogs, such as dihydroartemisinin, artemether, artesunate, artemiside, artemisone, and arteether, possess not only potent antimalarial activity but also anti-viral, antifungal, anticancer, and anti-inflammatory properties. In this review, we discuss the current understanding of how artemisinin and its analogs affect the immune system and immune-related diseases
2017
Thomas Efferth
Beyond malaria: The inhibition of viruses by artemisinin-type compounds
Biotechnol Adv. 2018 Nov 1;36(6):1730-1737.
Abstract
Natural products represent valuable chemical scaffolds for drug development. A recent success story in this context was artemisinin, which is not only active against malaria but also to other diseases. This raised the interest of artemisinin’s potential for drug repurposing. On the present review, we give an overview on artemisinin’s antiviral activity. There is good in vitro and in vivo evidence for the activity of artemisinin and its derivatives against DNA viruses of the Herpesviridae and Hepadnaviridae families such as cytomegaloviruses, human herpesvirus 6, herpes simplex viruses 1 and 2, Epstein-Barr virus and Hepatitis B virus. The evidence is weaker for Polyomaviruses and papilloma viruses. Weaker or no inhibitory activity in vitro has been reported for RNA viruses such as human immunodeficiency viruses 1 and 2, hepatitis C virus, influenza virus and others. Interestingly, the artemisinin derivative artesunate did not exert cross-resistance to ganciclovir-resistant HCMV and exerted synergistic inhibition in combination with several clinically established antiviral standard drugs. The antiviral activity of first generation artemisinin derivatives (e.g. artesunate, artemether, etc.) was enhanced by novel derivatives, including dimer and trimer molecules. First results on patients indicating activity in a subset of HCMV patients. Novel developments in the field of nanotechnology and synthetic biology to bioengineer microorganisms for artemisinin production may pave the way for novel drugs to fight viral infections with artemisinin-based drugs.
2020
D’Alessandro S, Scaccabarozzi D, Signorini L, Perego F, Ilboudo DP, Ferrante P, Delbue S.
The Use of Antimalarial Drugs against Viral Infection
Microorganisms. 2020 Jan 8;8(1):85. doi: 10.3390/microorganisms8010085. PMID: 31936284; PMCID: PMC7022795.Abstract
In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.
Keywords: antimalarial drugs; emerging infections; viruses.
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.
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)
This paper describes the protocols used in the treatment of Coronavirus in China, some of which incorporate Artemisia annua.
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.
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.
Siukan Law, Albert Wingnang Leung, Chuanshan Xu
Is the traditional Chinese herb “Artemisia annua” possible to fight against COVID-19?
Letter to the Editor of the review Integrative Medicine Research
Integrative Medicine Research. 2020 Sep;9(3):100474. doi: 10.1016/j.imr.2020.100474. Epub 2020 Jul 15. PMID: 32742919; PMCID: PMC7362865.
Dr Catherine Poisson-Benatouil
Action of Artemisia annua on adaptive immunity in COVID-19 infections
Concept Note n° 1. Maison de l’Artemisia, April 2020
Abstract
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) and anti HIV in vitro thanks to the flavonoids, quercetin and dicaffeoylquinic acids it contains. These molecules have been shown to inhibit the enzymatic activity of MERS-CoV-3 CLPro (MERSCoV- 3 chymotrypsin-like protease), an enzyme also 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 extremely 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
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
Artemisia Annua, EMMPRIN, CYP A, PAK 1 et les métalloprotéases
Note de synthèse n° 3, Maison de l’ArtemisiaText in french
Abstract
During COVID 19, after the initial viral penetration, via TMPRSS2 (serum protease) which triggers the activation of the ACE2 receptor (angiotensin-converting enzyme type 2 receptor), the virus enters the cell and then, during its maturation and intracytoplasmic penetration, it expresses Cyclophillin A (CyPA). This triggers the extra-membrane expression of basigin or CD147 or EMMPRIN and its intracytoplasmic activation. Basigin acts in an intra- and extra-membrane manner with numerous proteins. A third molecule, serine/threonine kinase (PAK1), whose expression is proportional to the activation of the ACE2 receptor, participates in the viral pathological process.
The activation of these molecules, which act outside and inside the cell, is at the origin of a cytokine cyclone and the amplification of the inflammatory reaction of the organism via an intense chemotactic activity leading to the activity and circulation of leukocytes and macrophages and finally an induction of metalloproteinases (MMP) whose inhibitors are overwhelmed in this pathological state. In addition, there is a sideration of the lymphocyte function.
All clinical signs resulting from this uncontrolled post-invasive inflammatory reaction and the activation of metalloproteinases and cytokines appear in the patient after a few days. At the same time, as the receptors are activated, viral replication continues.
Artemisia annua can stop this cycle of pathological reaction by acting effectively on several targets, in particular the TMPRSS2 receptor, by inhibiting its expression via androgenic receptors and thus the EMMPRIN activation cascade and its consequences. Some biomolecules of Artemisia annua (artemisinin and its derivatives, flavonoids, sesquiterpenes, polyphenols, quercetin) are also anti-inducers of metalloproteinases. This property has been especially exploited during anticancer treatment, pathologies where the expression of metalloproteases is also involved. Finally, artemisinin and its derivatives are natural inhibitors of PAK1.
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.
Matthew R Desrosiers, Alexis Mittelman, Pamela J Weathers
«Dried Leaf Artemisia Annua Improves Bioavailability of Artemisinin»2020 via Cytochrome P450 Inhibition and Enhances Artemisinin Efficacy Downstream
Biomolecules. 2020 Feb 7;10(2):254.
Abstract
Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, extracts, teas, and phytochemicals from DLA were tested and IC50 values for CYP2B6 and CYP3A4 were measured. For tissue distribution studies, artemisinin or DLA was orally delivered to rats, tissues harvested at 1 h, and blood, urine and feces over 8 h; all were analyzed for artemisinin and deoxyartemisinin by GC-MS. For inflammation, rats received an intraperitoneal injection of water or lipopolysaccharide (LPS) and 70 mg/kg oral artemisinin as pure drug or DLA. Serum was collected over 8 h and analyzed by ELISA for TNF-α, IL-6, and IL-10. DLA-delivered artemisinin distributed to tissues in higher concentrations in vivo, but elimination remained mostly unchanged. This seemed to be due to inhibition of first-pass metabolism by DLA phytochemicals, as demonstrated by HLM assays of DLA extracts, teas and phytochemicals. DLA was more effective than artemisinin in males at attenuating proinflammatory cytokine production; the data were less conclusive in females. These results suggest that the oral consumption of artemisinin as DLA enhances the bioavailability and anti-inflammatory potency of artemisinin.
Keywords: Artemisia annua; artemisinin; cytochrome P450 inhibition; inflammation; tissue distribution.
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
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
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.
Adhikari, Bikash; Marasini, Bishnu P.; Rayamajhee, Binod; Bhattarai, Bibek Raj; Lamichhane, Ganesh; Khadayat, Karan; Adhikari, Achyut; Khanal, Santosh; Parajuli, Niranjan
Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID19: A review
Phytotherapy Research (2020)
Abstract
The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.
Keywords anti-antiviral activity and COVID-19, drug candidates, natural products
Cheong DHJ, Tan DWS, Wong FWS, Tran T.
Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases
Pharmacol Res. 2020 Aug;158:104901. doi: 10.1016/j.phrs.2020.104901. Epub 2020 May 13. PMID: 32405226; PMCID: PMC7217791.
Abstract
Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its endoperoxidase properties. Progressively, research has found that artemisinins displayed multiple pharmacological actions against inflammation, viral infections, and cell and tumour proliferation, making it effective against diseases. Moreover, it has displayed a relatively safe toxicity profile. The use of artemisinins against different respiratory diseases has been investigated in lung cancer models and inflammatory-driven respiratory disorders. These studies revealed the ability of artemisinins in attenuating proliferation, inflammation, invasion, and metastasis, and in inducing apoptosis. Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis. In this review, we aim to provide a comprehensive update of the current knowledge of the effects of artemisinins in relation to respiratory diseases to identify gaps that need to be filled in the course of repurposing artemisinins for the treatment of respiratory diseases. In addition, we postulate whether artemisinins can also be repurposed for the treatment of COVID-19 given its anti-viral and anti-inflammatory properties.
Keywords: Arteether (PubChem CID: 3000469); Artemether (PubChem CID: 68911); Artemisinin; Artemisitene (PubChem CID: 11000442); Artesunate (PubChem CID:156252); COVID-19; Cell proliferation; Chemical compounds studied in this article Artemisinin (PubChem CID: 68827); Dihydroartemisinin (PubChem CID: 139073990); Inflammation; Lung; Respiratory diseases.Li, G.; Yuan, M.; Li, H.; Deng, C.;Wang, Q.; Tang, Y.; Zhang, H.; Yu, W.; Xu, Q.; Zou, Y.; et al.
Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: An open-label, non-randomized, and controlled trial.
Int J. Antimicrob. Agents 2020, 18, 106216.
Abstract
There are no effective therapies for patients with coronavirus disease-2019 (COVID-19). Methods Forty-one patients with confirmed COVID-19 were enrolled in the study and divided into two groups: artemisinin-piperaquine (AP) (n = 23) and control (n = 18). The primary outcome were the time taken to reach undetectable levels of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the percentage of participants with undetectable SARS-CoV-2 on days 7, 10, 14, and 28. The computed tomography (CT) imaging changes within 10 days, corrected QT interval changes, adverse events, and abnormal laboratory parameters were the secondary outcomes. Results The mean time to reach undetectable viral RNA (mean ± standard deviation) was 10.6 ± 1.1 days (95% confidence interval (CI) 8.4–12.8) for the AP group and 19.3 ± 2.1 days (95% CI 15.1–23.5) for the control group. The percentages of patients with undetectable viral RNA on days 7, 10, 14, 21, and 28 were 26.1%, 43.5%, 78.3%, 100%, and 100%, respectively, in the AP group and 5.6%, 16.7%, 44.4%, 55.6%, and 72.2%, respectively, in the control group. The CT imaging within 10 days post-treatment showed no significant between-group differences (P > 0.05). Both groups had mild adverse events.
Conclusions In patients with mild-to-moderate COVID-19, the time to reach undetectable SARS-CoV-2 was significantly shorter in the AP group than that in the control group. However, physicians should consider QT interval changes before using AP.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. Published online 2020 Jul 22.
2021 Oct;39(16):6184-6194. doi: 10.1080/07391102.2020.1796809. Epub 2020 Jul 22. PMID: 32696720; PMCID: PMC7441758
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.
Keywords: COVID-19; SARS-CoV-2; antiviral; artemisinin; hACE2; hydroxychloroquine; spike protein.
Sharma Shilpa, and Shashank Deep.
In-silico drug repurposing for targeting SARS-CoV-2 main protease (Mpro)
Journal of biomolecular structure & dynamics, 1-8. 12 Nov. 2020, doi:10.1080/07391102.2020.1844058
Abstract
COVID-19, caused by novel coronavirus or SARS-CoV-2, is a viral disease which has infected millions worldwide. Considering the urgent need of the drug for fighting against this infectious disease, we have performed in-silico drug repurposing followed by molecular dynamics (MD) simulation and MMGBSA calculation. The main protease (Mpro) is one of the best-characterized drug targets among coronaviruses, therefore, this was screened for already known FDA approved drugs and some natural compounds. Comparison of docking and MD simulation results of complexes of drugs with that of inhibitor N3 (experimentally obtained) suggests EGCG, withaferin, dolutegravir, artesunate as potential inhibitors of the main protease (Mpro). Further, in silico docking and MD simulation suggest that EGCG analogues ZINC21992196 and ZINC 169337541 may act as a better inhibitor.
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
Suhas G Kshirsagar. & Rammohan V Rao
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.
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
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.
Tegen D, Dessie K, Damtie D. Candidate Anti-COVID-19
Candidate Anti-COVID-19 Medicinal Plants from Ethiopia: A Review of Plants Traditionally Used to Treat Viral Diseases
Evid Based Complement Alternat Med. 2021 Jun 4;2021:6622410. doi: 10.1155/2021/6622410. PMID: 34221083; PMCID: PMC8219417.
Abstract
Background: Emerging viral infections are among the major global public health concerns. The pandemic COVID-19 is a contagious respiratory and vascular disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are no medicines that can treat SARS-CoV-2 except the vaccines. Therefore, searching for plant-originated therapeutics for the treatment of COVID-19 is required. Consequently, reviewing medicinal plants used to treat different viral infections is mandatory. This review article aims to review the ethnobotanical knowledge of medicinal plants traditionally used to treat different viral diseases by the Ethiopian people and suggests those plants as candidates to fight COVID-19.
Methods: Articles written in English were searched from online public databases using searching terms like "Traditional Medicine," "Ethnobotanical study," "Active components," "Antiviral activities," and "Ethiopia." Ethnobotanical data were analyzed using the Excel statistical software program.
Result: From the 46 articles reviewed, a total of 111 plant species were claimed to treat viral infections. Fifty-six (50.4%) of the plant species had reported to have antiviral active components that are promising to treat COVID-19. Lycorine, gingerol shogaol, resveratrol, rhoifolin, oleanolic acid, kaempferol, rosmarinic acid, almond oil, ursolic acid, hederagenin, nigellidine, α-hederin, apigenin, nobiletin, tangeretin, chalcone, hesperidin, epigallocatechin gallate, allicin, diallyl trisulfide, ajoene, aloenin, artemisinin, glucobrassicin, curcumin, piperine, flavonoids, anthraquinone, hydroxychloroquine, and jensenone were some of them.
Conclusion: The Ethiopian traditional knowledge applies a lot of medicinal plants to treat different viral infections. Reports of the chemical components of many of them confirm that they can be promising to fight COVID-19.
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 efficacy 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
Zhou Y, Gilmore K, Ramirez S, Settels E, Gammeltoft KA, Pham LV, Fahnøe U, Feng S, Offersgaard A, Trimpert J, Bukh J, Osterrieder K, Gottwein JM, Seeberger PH.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285423/
In vitro efficacy of artemisinin-based treatments against SARS-CoV-2.
Sci Rep. 2021 Jul 16;11(1):14571. doi: 10.1038/s41598-021-93361-y. PMID: 34272426; PMCID: PMC8285423.
Abstract
Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration-response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7-12 µg/mL), followed by artemether (53-98 µg/mL), A. annua extracts (83-260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
Rajan Rolta, Deeksha Salaria, Prem Prakash Sharma, Bhanu Sharma, Vikas Kumar, Brijesh Rathi, Mansi Verma, Anuradha Sourirajan, David J. Baumler, Kamal Dev.
Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit Spike Protein of SARS-CoV-2 Binding to ACE2 Receptor: In Silico Approach
Current Pharmacology Reports (2021) 7:4, 135-149.
Abstract
COVID-19, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and neutrapilin-1 receptors. Since Chloroquine has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and artemisinin for its interaction with spike proteins (6VXX, 6VYB) and its variant 7NXA, respectively. Molecular docking study of phytocompounds and SARS-CoV-2 spike protein was performed by using AutoDock/Vina software. Molecular dynamics (MD) simulation was performed for 50ns. Among all the phytocompounds, molecular docking studies revealed lowest binding energy of artemisinin with 6VXX and 6VYB, with Etotal -10.5 KJ mol-1 and -10.3 KJ mol-1 respectively. Emodin showed the best binding affinity with 6VYB with Etotal -8.8 KJ mol-1and SARS-CoV-2 B.1.351 variant (7NXA) with binding energy of -6.4KJ mol-1. Emodin showed best interactions with TMPRSS 2 and ACE2 with Etotal of -7.1 and -7.3 KJ mol-1 respectively, whereas artemisinin interacts with TMPRSS 2 and ACE2 with Etotal of -6.9 and -7.4 KJ mol-1 respectively. All the phytocompounds were non-toxic and non-carcinogenic. MD simulation showed that artemisinin has more stable interaction with 6VYB as compared to 6VXX, and hence proposed as potential phytochemical to prevent SARS-CoV-2 interaction with ACE-2 receptor.
Keywords: Antimalarial drugs; Artemisinin; COVID-19; Chloroquine; Emodin; In silico; MD simulation; Phytocompounds; Thymol.
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
Journal of Ethnopharmacology 274 (june 2021) 114016
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.
Yunjia Hu, Meiqin Liu, Hongbo Qin, Haofeng Lin, Xiaoping An, Zhengli Shi, Lihua Song, Xinglou Yang, Huahao Fan, and Yigang Tong
Artemether, Artesunate, Arteannuin B, Echinatin, Licochalcone B and Andrographolide Effectively Inhibit SARS-CoV-2 and Related Viruses In Vitro
Front Cell Infect Microbiol. 2021; 11: 680127.
Published online 2021 Aug 30. doi: 10.3389/fcimb.2021.680127Abstract
Since the first reported case caused by the novel coronavirus SARS-CoV-2 infection in Wuhan, COVID-19 has caused serious deaths and an ongoing global pandemic, and it is still raging in more than 200 countries and regions around the world and many new variants have appeared in the process of continuous transmission. In the early stage of the epidemic prevention and control and clinical treatment, traditional Chinese medicine played a huge role in China. Here, we screened out six monomer compounds, including artemether, artesunate, arteannuin B, echinatin, licochalcone B and andrographolide, with excellent anti-SARS-CoV-2 and anti-GX_P2V activity from Anti-COVID-19 Traditional Chinese Medicine Compound Library containing 389 monomer compounds extracted from traditional Chinese medicine prescriptions “three formulas and three drugs”. Our discovery preliminary proved the stage of action of those compounds against SARS-CoV2 and provided inspiration for further research and clinical applications. Keywords: COVID-19, SARS-CoV-2, GX_P2V, traditional Chinese medicine, antivirals
Chandramouli V, Niraj SK, Nair KG, Joseph J, Aruni W.
Phytomolecules Repurposed as Covid-19 Inhibitors: Opportunity and Challenges
Curr Microbiol. 2021 Oct;78(10):3620-3633.
doi: 10.1007/s00284-021-02639-x. Epub 2021 Aug 26. PMID: 34448061; PMCID: PMC8390070.
Abstract
The SARS-CoV-2 virus has spread worldwide to cause a full blown pandemic since 2020. To date, several promising synthetic therapeutics are repurposed and vaccines through different stages of clinical trials were approved and being administered, but still the efficacy of the drugs and vaccines are yet to be decoded. This article highlights the importance of traditional medicinal plants and the phytomolecules derived from them, which possess in vitro antiviral and anti-CoV properties and further explores their potential as inhibitors to molecular targets of SARS-CoV-2 that were evaluated by in silico approaches. Botanicals in traditional medicinal systems have been investigated for anti-SARS-CoV-2 activity through in silico and in vitro studies. However, information linking structure of phytomolecules to their antiviral activity is limited. Most phytomolecules with anti-CoV activity were studied for inhibition of the human ACE2 receptor through which the virus enters host cells, and non-structural proteins 3CLpro and PLpro. Although the proteases are ideal anti-CoV targets, information on plant-based inhibitors for the CoV structural proteins, e.g., spike, envelope, membrane, nucleocapsid required further investigations. In absence of scientific evaluations through in vitro and biocompatibility studies, plant-based antivirals fall short as treatment options. Plant-based anti-SARS-CoV-2 therapeutics can be promising alternatives to their synthetic counterparts as they are economical and bear fewer chances of toxicity, side effects, and viral resistance. Our review could provide a systematic overview of the potential phytomolecules which can be repurposed and subjected to further modes of experimental evaluation to qualify for use in treatment and prophylaxis of SARS-CoV-2 infections
Kubra Dogan, Ebru Erol, Muge Didem Orhan, Zehra Degirmenci, Tugce Kan, Aysen Gungor, Belkis Yasa, Timucin Avsar, Yuksel Cetin, Serdar Durdagi, Mustafa Guzel
Instant determination of the artemisinin from various Artemisiaannua L. extracts by LC-ESI-MS/MS and their in-silicomodelling and in vitro antiviral activity studies against SARS-CoV-2
Phytochemical Analysis. September 2021; 1–17.
Abstract
Introduction: Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS-CoV-2.
Objective: The main objective of our study was to determine artemisinin content byliquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS-CoV-2 using molecular modelling.
Methodology: Twenty-one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra-rapid determined artemisinin active molecules by LC-ESI-MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS-CoV-2virus was assessed by time resolved fluorescence energy transfer (TR-FRET) assay.
Results: Artemisinin content in the range 0.062–0.066%. Artemisinin showed signifi-cant inhibition of 3CL protease activity but not Spike/ACE-2 binding. The 50% effec-tive concentration (EC50) of artemisinin against SARS-CoV-2 Spike pseudovirus was found greater than 50 μM (EC45) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF-α production on both pseudovirus and lipopolysaccharide (LPS)-induced THP-1 cells were found significant in a dose dependent manner.
Conclusion: Further studies of these extracts for COVID-19 treatment will shed lightto seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.
Keywords: antiviral activity, Artemisia annua SARS-CoV-2, LC-ESI-MS/MS, natural products for COVID-19
M S Nair, Y Huang, D A Fidock, M J Towler, P J Weathers
Artemisia annua L. hot-water extracts show potent activity in vitro against Covid-19 variants including delta
J Ethnopharmacol. 2021 Nov 1:114797. doi: 10.1016/j.jep.2021.114797. Epub ahead of print. PMID: 34737005.Full text non available
Abstract
Ethnopharmacological relevance: For millennia, Artemisia annua L. was used in Southeast Asia to treat "fever". This medicinal plant is effective against multiple pathogens and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria caused by Plasmodium parasites.
Aim of the study: The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants.
Materials and methods: Using Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua L. extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1).
Results: In addition to being effective against the original wild type (WT) WA1, A. annua cultivars A3, BUR, MED, and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3 to 8.4 μM and 1.4-25.0 μM, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0 to 67.7 μg DW and 59.5-160.6 μg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 μg in the extract of any cultivar.
Conclusions: Results suggest that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.
Keywords: Artemisinin; Covid-19; Delta variant; Gamma variant; Kappa variant; SARS-CoV-2.
2022
Tang Y, Li X, Yuan Y, Zhang H, Zou Y, Xu Z, Xu Q, Song J, Deng C, Wang Q.
Network pharmacology-based predictions of active components and pharmacological mechanisms of Artemisia annua L. for the treatment of the novel Corona virus disease 2019 (COVID-19).
BMC Complement Med Ther. 2022 Mar 3;22(1):56. doi: 10.1186/s12906-022-03523-2. PMID: 35241045; PMCID: PMC8893058.Abstract
Background: Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19.
Methods: Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19.
Results: In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua’s potentially active compounds and targets associated with them that act against COVID-19.
Conclusions: These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.
Keywords: Artemisia annua L.; COVID-19; MM-GBSA; Molecular docking; Molecule dynamics; Network pharmacology.
Published online by
25/05/2020
https://lavierebelle.org/activites-antivirales-d-artemisia
25/05/2020
https://lavierebelle.org/activites-antivirales-d-artemisia
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