Molecular docking and dynamics simulation study of medicinal fungi derived secondary metabolites as potential inhibitor for COVID-19 treatment

Abstract

The severity of COVID-19, lack of specific treatment, and controversies on the vaccine's efficacy demand the development of new drugs against SARS-CoV-2. Fungi produce various metabolites with diverse molecular structures that have emerged as promising antiviral drug candidates. Therefore, the present study aimed to investigate medicinal fungi derived secondary metabolites as potential inhibitors of 3 different targets associated with viral entry (human TMPRSS2) and replication (main and papain-like protease) through molecular docking and dynamic simulation studies. Based on our findings, we identified Phelligridin E, Lepiotaprocerine G, and Inoscavin A as the potential blockers of SARS-CoV-2 main protease, papain-like protease, and human TMPRSS2, respectively. These compounds strongly interacted with their corresponding target, passed Lipinski Rule's and had acceptable ADMET properties. Drug-protein complexes showed good stability during MD simulation. Estimation of binding free energy using the MM-GBSA method validated the inhibitor potential of identified compounds. Taken together, we believe that further in vitro and in vivo investigations on our proposed molecules may contribute to expanding the therapeutic arsenal in our fight against COVID-19.

Keywords

• SARS-CoV-2
• COVID-19
• Medicinal fungi
• Metabolites
• Docking simulation