Structure-based computational screening and molecular dynamics reveal potential inhibitors of Norovirus VP1 and RdRp Proteins: an in-silico study

Norovirus is recognized as a pathogen with pandemic potential, exhibiting a higher fatality rate in low-income countries, particularly affecting young children. Currently, vaccine or specific antiviral treatment for norovirus is lacking. For evaluating antiviral compounds, this study was conducted by targeting viral protein 1 (VP1) and RNA-dependent RNA polymerase (RdRP) proteins through in silico approach, which included modeling protein, assessment stability, molecular docking, molecular simulation, non-covalent interaction (NCI) analysis, and pharmacokinetic profiling. Higher binding affinity revealed by molecular docking (-7.8 kcal/mol to -9.4 kcal/mol) for the ligands Zingiberol, Cardeonolide, Boeravinone B, Beta-Elemene, and Fisetin with VP1 and RdRp. The molecular dynamic simulation and subsequent analyses demonstrated significantly expected stable docked complexes of the protein-ligand in comparison to the ribavirin antiviral drug. Furthermore, these ligands exhibited acceptable drug-likeness and ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) profiles. This study initially suggests that these compounds have potentiality as antiviral candidates, warranting wet lab experiment to be considered for norovirus infection.