In a recent bioRXiv pre- press document , scholars from Germany, Denmark and Hong Kong report the in vitro efficacy of the extracts of the Artemisia annua plant , but also of artemisinin, artesunate and artemether derivatives against severe acute respiratory syndrome. Coronavirus (SARS-CoV-2) .

The pandemic caused by SARS-CoV-2 has caused more than one million deaths worldwide from Coronavirus disease (COVID-19). This respiratory and systemic disease is highly contagious and, in many cases, life-threatening.

And while we look forward to an effective vaccine, there is an urgent need to discover effective antivirals against SARS-CoV-2. One of the most effective approaches that have been used since the beginning has been to reuse drugs already authorized for other diseases.

Purified bioactive extracts and compounds of the Artemisia annua plant (especially artemisinin, artesunate and artemether) are found in various combination therapies used to successfully treat malaria , as they are known to rapidly reduce parasite burden in infected individuals.

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

Consequently, a multinational research group led by Dr Kerry Gilmore of 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 some activity against SARS-CoV-2 under laboratory conditions.

Evaluation of synthetic extracts and compounds

At the start of the study, several extracts of Artemisia annua , but also artemisinin, were screened for antiviral activity using a plaque reduction test in a pretreatment setting. A German strain of SARS-CoV-2 from Munich was used for this.

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

High-throughput antiviral assays enabled drug concentrations to be tested in multiple replicates, which yielded accurate EC50 values ​​(i.e., the concentration of a compound that provides a semi-maximal response).

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

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

Results of pretreatment and treatment tests

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 an EC50 of 7 µg / mL) was more potent than the plant extracts tested (128-260 µg / mL), artemisinin (151 µg / mL) or artemether (more than 179 µg / mL) in the treatment while the EC50 values ​​in the pretreatment assays were generally slightly higher.

Furthermore, the selectivity index (which is calculated on the basis of treatment and cell viability tests) was higher for artemisinin and roughly the same for extracts, artesunate and artemether. It should be noted that the results obtained in human Huh7.5 hepatoma cells were similar to those of the Vero E6 cell line.

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

Will it be clinically useful?

“In our study, we confirm the efficacy of the artemisinin-based treatment for two European strains of SARS-CoV-2 from Germany and Denmark, which are most closely related to the majority of SARS-CoV-2 strains circulating throughout the world compared to the Wuhan strain, ”the study authors highlight in this bioRxiv document .

However, if we translate these results into clinical conditions, only artesunate showed EC50 values ​​in the range of clinically achievable plasma and tissue concentrations between the tested extracts and the pure compounds.

Therefore, further studies are certainly needed to adequately assess the usefulness of these compounds as a potential treatment option for COVID-19. Likewise, any recommendations for taking mugwort extract should await validation of the concept in controlled clinical trials.

*Important Notice

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