Naphthoquinones from Onosma: Molecular Mechanisms of Action in the Treatment and Prevention of COVID-19

Abstract

Absrtact COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in December 2019 in Wuhan, China. There is currently no effective treatment or immunization for the virus, and it is spreading rapidly with a high mortality rate. As a crucial CoV enzyme involved in initiating both viral replication and transcription, the COVID-19 main protease (Mpro) is an appealing target for researchers. Novel therapeutics are urgently required to treat the early stages of COVID-19 caused by SARS-CoV-2. Therefore, to find potential COVID-19 Mpro inhibitors, naphthoquinones from the Onosma genus were screened to find out their possible effects on the Mpro enzyme. In this study, we employed a range of computational approaches, including molecular docking and MM-GBSA, to uncover potential inhibitors of SARS-CoV-2 Mpro from existing natural product databases. According to our findings, the molecules deoxyshikonin, 3-hydroxy-isovalerylshikonin, propionylshikonin, and acetylshikonin have high binding affinities for the Mpro enzyme. In addition, it was observed that the other shikonin compounds have anti-Mpro enzyme activity. Docking simulations and molecular mechanics suggest that shikonin derivatives might be effective anti-SARS-CoV-2 compounds.