Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents-A Pharmacoinformatic-Based Approach

Oluwakemi Ebenezer; Nkululeko Damoyi; Maryam A Jordaan; Michael Shapi

doi:10.3390/molecules27020380

Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents-A Pharmacoinformatic-Based Approach

Molecules. 2022 Jan 7;27(2):380. doi: 10.3390/molecules27020380.

Authors

Oluwakemi Ebenezer¹, Nkululeko Damoyi¹, Maryam A Jordaan¹, Michael Shapi¹

Affiliation

¹ Department of Chemistry, Faculty of Natural Science, Mangosuthu University of Technology, 511 Mangosuthu Highway, Durban 4000, South Africa.

Abstract

The RNA-dependent RNA polymerase (RdRp) receptor is an attractive target for treating human norovirus (HNV). A computer-aided approach like e-pharmacophore, molecular docking, and single point energy calculations were performed on the compounds retrieved from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database to identify the antiviral agent that could target the HNV RdRp receptor. Induced-fit docking (IFD) results showed that compounds ZINC1617939, ZINC1642549, ZINC6425208, ZINC5887658 and ZINC32068149 bind with the residues in the active site-B of HNV RdRp receptor via hydrogen bonds, salt bridge, and electrostatic interactions. During the molecular dynamic simulations, compounds ZINC6425208, ZINC5887658 and ZINC32068149 displayed an unbalanced backbone conformation with HNV RdRp protein, while ZINC1617939 and ZINC1642549 maintained stability with the protein backbone when interacting with the residues. Hence, the two new concluding compounds discovered by the computational approach can be used as a chemotype to design promising antiviral agents aimed at HNV RdRp.

Keywords: human norovirus; molecular dynamic; multiple docking; virtual screening.

MeSH terms

RNA-Dependent RNA Polymerase*

Substances

RNA-Dependent RNA Polymerase