Key result
Computational screening identifies two pyrimidindinone compounds that stably bind HNV RdRp as potential anti-norovirus agents.
Why the study?
The RNA-dependent RNA polymerase receptor is an attractive target for treating human norovirus.
In silico screening identified two compounds (ZINC1617939 and ZINC1642549) that stably bind the human norovirus RdRp receptor, serving as potential chemotypes for novel antivirals.
These in silico hits require experimental validation; leaves open therapeutic potential against norovirus.
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.
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Ebenezer et al. (2022) studied Human norovirus (HNV). Pyrimidindinones (ZINC1617939, ZINC1642549) was evaluated on Binding affinity and stability with HNV RdRp. Computational screening identified pyrimidindinone compounds ZINC1617939 and ZINC1642549 as potential anti-norovirus agents that stably bind to the active site of the HNV RdRp receptor.
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