Euphorbia hirta compound inhibits SARSCoV-2 main protease: in silico molecular docking and ADME studies

Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 virus is responsible for a myriad of deaths globally. There is currently no cure for it, and clinical trials are still on-going for vaccine production. Medicinal plants with good antiviral properties may serve as alternative treatment for COVID-19. The main protease (Mpro) has become an attractive drug target against SARS-CoV-2 in many pieces of research for the development of COVID-19 drugs, and with the absence of closely related human proteases having protease inhibitors that are unlikely to be harmful due to their similar cleavage specificity. Euphorbia hirta has been reported to exhibit antiviral activity. The inhibition of the proteolytic activity of SARS-CoV-2 Mpro by bioactive constituents in Euphorbia hirta may disrupt viral replication. In light of this, the current study investigated inhibition of SARS-CoV-2 Mpro by compounds found in Euphorbia hirta. Secondary metabolites from the plant were mined and molecular docking protocols, using Schrödinger Suite was used to evaluate the compounds for best inhibition properties using Remdesivir as standard. Docking results revealed that ellagic acid (EA) had higher binding affinity -8.608 kcal/mol, compared to Remdesivir (-7.739 kcal/mol). EA also made contact with important amino acids in the active site of the protein via hydrogen bonding. ADME properties of EA were within acceptable ranges, and none of Lipinski's rules were violated. In conclusion, EA could be a potential drug candidate for combating the COVID-19 pandemic by targeting the SARS-CoV-2 Mpro.