Study reveals potential utility of artemisinin-based treatments against SARS-CoV-2

In a recent, methodologically robust bioRXiv* preprint paper, researchers from Germany, Denmark and Hong Kong report in vitro efficacy of extracts from the sweet wormwood plant (Artemisia annua), but also artemisinin, artesunate, and artemether derivatives against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2. Image Credit: Topimages / Shutterstock
Study: In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2. Image Credit: Topimages / Shutterstock

The pandemic caused by the SARS-CoV-2 has caused over one million deaths worldwide due to coronavirus disease 2019 (COVID-19). This respiratory and systemic illness is very contagious and, in many instances, life-threatening.

And while we eagerly wait for an effective vaccine, there is an urgent need to discover effective antivirals against SARS-CoV-2. One of the more effective approaches that have been used since the start was to repurpose drugs that are already licensed for other diseases.

Extracts and purified bioactive compounds from the plant Artemisia annua (most notably artemisinin, artesunate and artemether) are found in various combination therapies that are used to successfully treat malaria, since they are known to rapidly reduce the parasite burden in the infected individuals.

Due to their excellent safety profile with rare side effects, low cost, and distribution readiness, artemisinin-based drugs could indeed be attractive repurposing candidates for the treatment of COVID-19.

Consequently, a multinational research group led by Dr. Kerry Gilmore from the Max Planck Institute for Colloids and Interfaces in Potsdam, Germany, set out to determine whether Artemisia annua extracts, as well as pure artemisinin, artesunate and artemether have certain activity against SARS-CoV-2 in the laboratory conditions.

Appraising extracts and synthetic compounds

At the beginning of the study, several Artemisia annua extracts, but also artemisinin were screened for antiviral activity by employing a plaque-reduction assay in a pretreatment setting. For that purpose, a German SARS-CoV-2 strain from Munich has been used.

Based on these findings, the researchers selected three extracts and pure, synthetic artemisinin, artesunate and artemether to study in detail. Concentration-response curves were established for extracts and compounds for pretreatment and treatment settings by utilizing a Danish SARS-CoV-2 strain from Copenhagen.

High-throughput antiviral assays enabled testing of drug concentrations in multiple replicates, which resulted in accurate EC50 values (i.e., the concentration of a compound that gives half-maximal response).

Finally, human Huh7.5 hepatocyte-derived carcinoma cell line was used to confirm the EC50 determined in Vero E6 cells (the latter being kidney epithelial cells extracted from an African green monkey).

In short, after the incubation period, the infected cells were visualized by immunostaining for SARS-CoV-2 spike glycoprotein (at room temperature) and counted automatically. Cell viability has also been monitored in detail.

Results of the pretreatment and treatment assays

This study revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of Vero E6 cells. More specifically, artesunate (with EC50 of 7 µg/mL) was more potent than the tested plant extracts (128-260 µg/mL), artemisinin (151 µg/mL), or artemether (more than 179 µg/mL) in treatment assays, whereas generally EC50 values in pretreatment assays were somewhat higher.

Moreover, the selectivity index (which is calculated based on treatment and cell viability assays) was highest for artemisinin and roughly equal for the extracts, artesunate, and artemether. It has to be noted that the results obtained in human hepatoma Huh7.5 cells were similar to those in Vero E6 cell line.

The researchers also emphasize that the extracts utilized in this study were prepared from plants that are grown under standardized and optimized conditions, following a procedure where concentrations of the extracted material are reproducible.

Will it be clinically useful?

"In our study, we confirm the efficacy of artemisinin-based treatment for two European SARS-CoV-2 strains from Germany and Denmark, which are more closely related to the majority of SARS-CoV-2 strains circulating worldwide than the Wuhan strain", highlight study authors in this bioRxiv paper.

Nonetheless, if we translate these findings to clinical conditions, only artesunate showed EC50 values in the range of clinically achievable plasma and tissue concentrations among the tested extracts and pure compounds.

Hence, further studies are definitely required to adequately evaluate the utility of these compounds as a potential COVID-19 treatment option. Likewise, any recommendations to take sweet wormwood extract should wait concept validation in controlled clinical trials.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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Comments

  1. Mateon Therapeutics Mateon Therapeutics United States says:

    Max Planck Institute's data on Artemisinin is in agreement with our previously reported SARS-COV-2 antiviral activity of purified Artemisinin vs. Artemesia extract.  Based on the in vitro data and anectodal clinical data we have launched a global interventional study to evaluate the Artemisinin versus COVID-19.  The drug product was also approved by India's AYUSH ministry.

    investor.mateon.com/.../mateon-announces-first-patient-enrolled-arti-19-multicenter

    investor.mateon.com/.../mateon-therapeutics-initiate-commercialization-artishieldtm

    We encourage collaboration among the various stakeholders to quickly arrive at a cure for COVID-19.

    Regards
    Vuong Trieu PhD
    CEO/Mateon Therapeutics

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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