Exploring the potential of novel phenolic compounds as potential therapeutic candidates against SARS-CoV-2, using quantum chemistry, molecular docking and dynamic studies

Abstract

In the current study, the interaction of SARS-CoV-2 protein (A and B chains of nsp13) with different recently synthesized phenolic compounds (Sreenivasulu et al., Synthetic Communications, 2020, 112-122) has been studied. The interactions have been investigated by using molecular docking, quantum chemical and molecular dynamics simulations methods. The molecular structures of all the ligands are studied quantum chemically in terms of their optimized structures, 3-D orbital distributions, global chemical descriptors, molecular electrostatic potential plots and HOMO-LUMO orbital energies. All the ligands show reasonably good binding affinities with nsp-13 protein. The ligand L2 shows to have better binding affinities to Chain A and Chain B of nsp13 protein, which are -6.7 and -6.4 kcal/mol. The study of intermolecular interactions indicates that L2 shows different hydrophobic and hydrogen bond interactions with both chains. Furthermore, molecular dynamic simulations of the nsp13-L2 complex are obtained over a time scale of 60 ns, which indicates its stability and flexibility behavior as assessed in terms of its RMSD and RMSF graphs. The ADMET analysis also shows no violation of Lipinski rule (RO5) by studied phenolic compounds. We believe that the current findings will be further confirmed by in vitro and in vivo studies of these recent phenolic compounds for their potential as inhibitors for SARS-Co-V-2 virus.

Keywords: ADMET; Molecular docking; Molecular dynamics; Phenolic compounds; SARS-CoV-2.