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

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 (DT...

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Veröffentlicht in:Molecules (Basel, Switzerland) Jg. 27; H. 2; S. 380
Hauptverfasser: Ebenezer, Oluwakemi, Damoyi, Nkululeko, Jordaan, Maryam A., Shapi, Michael
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 07.01.2022
MDPI
Schlagworte:
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Antiviral drugs
Binding sites
Cell culture
Clinical trials
Enzymes
Genomes
human norovirus
Humans
Hydrogen Bonding
Infections
Ligands
Molecular Docking Simulation
molecular dynamic
Molecular Dynamics Simulation
multiple docking
Norovirus
Norovirus - drug effects
Protein Binding
Proteins
Pyrimidines - chemistry
Pyrimidines - pharmacology
RNA polymerase
RNA-Dependent RNA Polymerase - antagonists & inhibitors
RNA-Dependent RNA Polymerase - chemistry
RNA-Dependent RNA Polymerase - metabolism
Software
Toxicity
virtual screening
Viruses
United States > US
multiple docking
human norovirus
virtual screening
molecular dynamic
ISSN:1420-3049, 1420-3049
Online-Zugang:Volltext
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Zusammenfassung: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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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27020380