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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 …