Identification of Marine Fungi-Based Antiviral Agents as Potential Inhibitors of SARS-CoV-2 by Molecular Docking, ADMET and Molecular Dynamic Study

Abstract

The ongoing eruption of the COVID-19 pandemic instigated by severe-acute-respiratory-syndrome-coronavirus 2 (SARS-CoV-2) has produce enormous damage to the world. The need of the hour is to stop this pandemic by inhibiting the main protease (MPro) of SARS-CoV-2, which is primarily involved in viral replication. Our study aims to find potential inhibitors for MPro by docking marine fungi-based 90 antiviral compounds against SARS-CoV-2. Among these, 11 antiviral compounds (obeying Lipinski RO5) are selected from 90 docked antiviral compounds on the basis of binding energy range ([Formula: see text]6.4[Formula: see text]kcal/mol to [Formula: see text]9[Formula: see text]kcal/mol) and low inhibition constant values (0.23[Formula: see text][Formula: see text]M to 2.5[Formula: see text][Formula: see text]M) as compared with remdesivir (reference compound) toward MPro of SARS-CoV-2. Tryptoquivaline F, arisugacin B, and arisugacin A antiviral compounds exhibited effective hydrogen and hydrophobic (alkyl, [Formula: see text]-alkyl, and [Formula: see text]-anion) interactions and are expected to be potential protease inhibitors. Drug-likeness of these lead compounds are elaborated by boiled-egg and bioavailability radar map. The toxicity profile showed that the lead compounds L1, L2, and L3 have no AMES toxicity, skin sensitization, and cardiac toxicity. The RMSD graph proposed that all the complexes, i.e. L1, L2, and L3 are in the adequate RMSD range with the average value of 2.1[Formula: see text]Å. All the complex systems of L1, L2, and L3 showed fluctuations in the acceptable RMSF range of 1.5[Formula: see text]Å to 3[Formula: see text]Å. The molecular dynamics simulation proved the stability of docked complexes L1, L2, and L3 in the binding pocket of main protease. The average hydrogen count of all complexes is [Formula: see text], [Formula: see text], and [Formula: see text] H-bonds. The complexes L1-MPro, L2-MPro, and L3-MPro have an average value of [Formula: see text] as 22.44[Formula: see text]Å, 22.63[Formula: see text]Å, and 22.50[Formula: see text]Å, respectively. The lead compounds L1 (tryptoquivaline F), L2 (arisugacin b), and l3 (arisugacin A) in this study are the most promising inhibitors of SARS-CoV-2 main protease MPro, which are not reported in ealier studies. Our findings will evoke the scientific interest for their further in vitro and in vivo experimental studies.