In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19

TL;DR

This study used computational methods to identify phytochemicals from limonoids and triterpenoids as potential inhibitors of SARS-CoV-2 proteins, suggesting candidates for drug development and traditional medicine use.

Contribution

It is the first comprehensive in silico screening of limonoids and triterpenoids against multiple SARS-CoV-2 targets for potential COVID-19 therapeutics.

Findings

Identified phytochemicals effective against SARS-CoV-2 proteins

Demonstrated binding interactions at active sites of target proteins

Suggested medicinal plants for traditional therapeutic approaches

Abstract

Virtual screening of phytochemicals was performed through molecular docking, simulation, in silico ADMET and drug-likeness prediction to identify the potential hits that can inhibit the effects of SARS-CoV-2. Considering the published literature on medicinal importance, total 154 phytochemicals with analogous structure from limonoids and triterpenoids were selected to search potential inhibitors for the five therapeutic protein targets of SARS-CoV-2, i.e., 3CLpro (main protease), PLpro (papain-like protease), SGp-RBD (spike glycoprotein-receptor binding domain), RdRp (RNA dependent RNA polymerase) and ACE2 (angiotensin-converting enzyme 2). The in silico computational results revealed that the phytochemicals such as glycyrrhizic acid, limonin, 7-deacetyl-7-benzoylgedunin, maslinic acid, corosolic acid, obacunone and ursolic acid were found to be effective against the target proteins of SARS-CoV-2. The protein-ligand interaction study revealed that these phytochemicals bind with the amino acid residues at the active site of the target proteins. Therefore, the core structure of these potential hits can be used for further lead optimization to design drugs for SARS-CoV-2. Also, the medicinal plants containing these phytochemicals like licorice, neem, tulsi, citrus and olives can be used to formulate suitable therapeutic approaches in traditional medicines.