In silico Study of Antiviral Phytochemicals for the Potential Drug Development Against Wild-type and Omicron Variants of SARS-CoV-2.

Abstract

Aims: To identify potential phytochemical-based drugs for both wild-type and Omicron variants of SARS-CoV-2 using virtual screening and molecular dynamic simulation.

Background: Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by SARS-CoV-2. Since 2019, multiple variants have been reported from all over the world and the emergence of new variants of SARS-CoV-2 is a major concern.

Objective: To identify potential phytochemicals that can be used as drugs against different variants of SARS-CoV-2.

Methods: In our present study, we have selected 594 phytochemicals and performed virtual screening to identify potential drug candidates. The screening commenced with molecular docking techniques with both ACE2 (Human) and Spike protein (wild-type and Omicron variant), followed by prediction of pharmacokinetics parameters and toxicity. The Schrodinger tools, Swiss ADME, and ProTox-II accomplish the analysis. Further, molecular dynamics simulation, binding free energy calculation and meta-dynamics study was performed for best protein-ligand complexes of both proteins using GROMACS and gmx_MMPBSA to validate the stability of the docked complexes.

Results: we have identified 6 and 4 drugs as spike protein inhibitors for wild-type and Omicron variants, respectively. 6 drugs were identified as ACE2 receptor inhibitors. We have identified silymarin as a common drug inhibitor for both pathogen (Wild-type, and Omicrons spikes) as well as host (human ACE2) protein that reflects its ability to inhibit the host-pathogen interaction and prevent infection.

Conclusion: We have found some potential Phytochemicals that can be used against different variants of SARS-CoV-2 such as silymarin.