In-silico analysis of antiviral fungal inhibitors against Mpro receptor protein

The COVID-19 crisis prompted the rapid determination of protein structures using homologous modelling from SARS-CoV data. Drug repurposing is a promising strategy, leveraging existing research to identify potential compounds for treatment amidst the urgency of the pandemic. Based on the involvement in virus replication as well as anticipated non-interactive capability to attach with any target proteins of the virus, main protease (Mpro) is regarded as a potential antiviral therapeutic molecule among all other reported structures connected to SARS-CoV-2. Fungal metabolites are a reservoir of bioactive molecules that could be used for treating this new COVID-19 virus and minimal research on the same has been carried out to date. Thus, in this study, the aim is to identify possible naturally obtained fungal metabolites that can interact as well as decrease the activities of the Mpro receptor using in-silico analysis. Forty-five compounds possessing antiviral activity were taken for inspection and were further analyzed via Lipinski’s rule. Further, on executing molecular docking and dynamic studies on selected compounds, Sansalvamide A and ergosterol-5,8-peroxide are proposed to be a potential inhibitor of the Mpro receptor as they showed the least binding energy of − 9.01 kcal/mol and − 8.97 kcal/mol respectively. In molecular dynamics simulations, Ergosterol-5,8-peroxide showed stable RMSD values (maximum deviation: 2.4 Å), indicating protein stability, while Sansalvamide A exhibited fluctuating RMSD values (maximum deviation: 2.8 Å). Sansalvamide A displayed consistent interaction dynamics with GLU166, forming hydrogen bonds and water bridges, whereas Ergosterol-5,8-peroxide primarily interacted with GLY143 and SER144 through hydrogen bonding. Sansalvamide A demonstrated superior secondary structure element (SSE) formation (41.58%) compared to  Ergosterol-5,8-peroxide (37.12%). This indicates that both the compounds are the probable inhibitors of Mpro receptor and they should undergo in-vitro studies to support these assertions.