Structure-Based Virtual Screening of Antiviral Compounds Targeting the Norovirus RdRp Protein

Abstract

Background: Human noroviruses (NV) are the primary etiological organisms causing acute gastroenteritis around the world, causing severe morbidity and imposing a significant economic burden. The RNA-dependent RNA polymerase (RdRp) is essential for viral replication and could be a promising target for anti-NV therapeutics. Despite the discovery of a few NV RdRp inhibitors, the majority of these pharmaceuticals have demonstrated limited efficacy in inhibiting viral replication in cellular models.Methods: In this study, computational screening of antiviral compounds was conducted targeting the NV RdRp protein. The assessment was based on binding poses and the key residues of RdRp involved in interactions with compounds.Results: The compounds namely, Ribavirin, BMS806, Dihydromyricetin, R7935788, and LY2784544 were found to bind the RdRp protein with high affinity. Notably, these compounds displayed significantly lower binding affinities compared to the positive control, PPNDS. In addition, these compounds exhibited many RdRp protein binding residues that were also present in the PPNDS.Conclusion: The results presented here suggest that these compounds have the potential to be used as inhibitors of NV RdRp in the development of antiviral medications. Nevertheless, due to the computational nature of this study, it is imperative to do experimental validation.Keywords: Noroviruses; RdRp; Virtual screening; Antiviral Compounds