Exploration of Some Naturally Occurring Fungal-Derived Bioactive Molecules as Potential SARS-CoV-2 Main Protease (MPro) Inhibitors ThroughIn-silicoApproach

Abstract

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) main protease (MPro) is recognized as an important therapeutic target protein in the drug development for COVID-19. To date, clinical trials of many vaccine and other viral protease inhibitors (PI) are currently under investigation. Undoubtedly, there are chances of possible side effects and ineffectiveness. Thus, the search for natural bio-active molecules is of great interest that will exert antiviral activity as well as have least chances of toxicity. Fungi are considered as bio-enriched source of producing antiviral compounds. This study is focused on identifying potential fungal derived antiviral molecules with good binding affinity against SARS-CoV-2 MProusing molecular docking. Semicochliodinol B was identified as the best lead molecule with higher binding affinity ([Formula: see text][Formula: see text]kcal/mol) as compared to the co-crystalized ligand ([Formula: see text][Formula: see text]kcal/mol). The results of molecular docking confirm the hydrogen bond interaction of Semicochliodinol B with Glu166 and Asn142 as well as hydrophobic interactions with 20 amino acid residues of SARS-CoV-2 MPro. Semicochliodinol B also exhibited good binding affinity against SARS-CoV MProand Middle east respiratory syndrome-related corona virus (MERS-CoV MPro), suggesting its broad-spectrum activity. Druglikeness, Absorption, distribution, metabolism, excretion (ADME) and toxicity studies also directed that Semicochliodinol B may become a promising drug candidate and thus it can be further investigated as a potential inhibitor of SARS-CoV-2 MPro.