Cited by 122Medicinal Plant ResearchSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

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Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants

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Nair, M.S., Huang, Y., Fidock, D.A., Polyak, S.J., Wagoner, J., Towler, M.J., Weathers, P.J.·2021·Journal of Ethnopharmacology

DOI 10.1016/j.jep.2021.114016PMC PMC7952131

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Abstract

Ethnopharmacological relevance Artemisia annua L. has been used for millennia in Southeast Asia to treat "fever". Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria.Aim of the study SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2.Materials and methods Using Vero E6 and Calu-3 cells, we measured anti SARS-CoV-2 activity against fully infectious virus of dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as the concentrations that inhibited viral replication by 50%; CC50s were also calculated and defined as the concentrations that kill 50% of cells.Results 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. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet its hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC 50 of about 70 μM, and the clinically used 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. 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 above the antiviral IC 90 values.Conclusions A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.

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Authors: Nair, M. S., Huang, Y., Fidock, D. A., Polyak, S. J., Wagoner, J., Towler, M. J., & Weathers, P. J.
Affiliations: Aaron Diamond AIDS Research Center (US)
Columbia University Irving Medical Center (US)
University of Washington (US)
Worcester Polytechnic Institute (US)
Corresponding author: Nair, M.S.
Weathers, P.J.
ORCID: Nair, M.S.
Huang, Y.
Fidock, D.A.
Polyak, S.J.
Weathers, P.J.
Venue: Journal of Ethnopharmacology
Publisher: Elsevier BV
Published: 2021-06
Volume: 274
Pages: 114016
ISSN: 0378-8741 (ISSN-L)
DOI: 10.1016/j.jep.2021.114016
PMC: PMC7952131
OpenAlex: W3134666776
Cited by: 122
References: 42
Citations by year: 2026: 7 · 2025: 12 · 2024: 19 · 2023: 29 · 2022: 40 · 2021: 15
FWCI: 15.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 295 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Journal of Ethnopharmacology (acceptedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: Artemisia annua, SARS-CoV-2, COVID-19 pandemic, artemisinin, antiviral activity, plant extracts, viral replication inhibition, SARS-CoV-2 variants, Alpha variant, Beta variant, flavonoids, artemisinin derivatives, amodiaquine, cytotoxicity, medicinal plants
MeSH terms: COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antiviral Agents, Cell Line, Chlorocebus aethiops, Flavonoids, Humans, Plant Extracts, Vero Cells, Virus Replication, Plant Leaves, Artemisia annua, Artemisinins, Cell Line, Tumor, Spike Glycoprotein, Coronavirus

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Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants

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