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

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 (M-Pro) of SARS-CoV-2, which is primarily involved in viral replication. Our study aims to find potential inhibitors for M-Pro 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 (-6.4kcal/mol to -9kcal/mol) and low inhibition constant values (0.23 mu M to 2.5 mu M) as compared with remdesivir (reference compound) toward M-Pro of SARS-CoV-2. Tryptoquivaline F, arisugacin B, and arisugacin A antiviral compounds exhibited effective hydrogen and hydrophobic (alkyl, pi-alkyl, and pi-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 angstrom. All the complex systems of L1, L2, and L3 showed fluctuations in the acceptable RMSF range of 1.5 angstrom to 3 angstrom. 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 L1=69.5, L2=67.7, and L3=68.6 H-bonds. The complexes L1-M-Pro, L2-M-Pro, and L3-M-Pro have an average value of Rg as 22.44 angstrom, 22.63 angstrom, and 22.50 angstrom, 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 M-Pro, which are not reported in ealier studies. Our findings will evoke the scientific interest for their further in vitro and in vivo experimental studies.