Key result
In silico screening identified ZINC66112069 and ZINC69481850 as potential inhibitors of Human Norovirus RdRp, with binding energies of -9.7 and -9.4 kcal/mol compared to -9.0 kcal/mol for the control.
Why the study?
Human norovirus lacks approved treatments or vaccines, and existing RNA-dependent RNA polymerase inhibitors generally exhibit poor cell penetrability and drug-likeness.
Absolute Event Rate: -9.7% vs -9%
In silico screening identified ZINC66112069 and ZINC69481850 as potential inhibitors of Human Norovirus RdRp with favorable binding energies and stability.
These hits are hypothesis-generating; experimental validation required before any therapeutic consideration.
Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.
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Obaid et al. (2023) studied Human Norovirus (Gastroenteritis). ZINC66112069 and ZINC69481850 vs. PPNDS (positive control) was evaluated on Binding energy with RdRp. In silico screening identified ZINC66112069 and ZINC69481850 as potential inhibitors of Human Norovirus RdRp, with binding energies of -9.7 and -9.4 kcal/mol compared to -9.0 kcal/mol for the control.
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