Identification of Co-29, a 5-cyano-2-thiacetyl aromatic pyrimidinone, as a potential inhibitor targeting the RdRp of norovirus
Background Human norovirus (HNV) is the predominant pathogen causing outbreaks of acute gastroenteritis globally. Despite significant efforts to combat norovirus infections, there is currently no FDA approved vaccine or antiviral drug available. Consequently, the development of effective antiviral agents is of critical importance. Methods and results In this study, a series of 41 5-cyano-2-thiacetyl aromatic pyrimidinone compounds were designed and synthesized. A cell viability-based screening for anti-murine norovirus (MNV) compounds was conducted, revealing that compound 29 (hereafter used as Co-29) exhibited antiviral activity against MNV. Co-29 demonstrated effective inhibition of MNV CW3 RNA replication, exhibiting an EC 50 of 58.22 μM. An RdRp enzyme activity assay indicated that Co-29 directly inhibits RdRp activity to both MNV and HNV. Molecular docking studies suggested that Co-29 interacts with the palm region of RdRp via hydrogen bonding with specific residues, which are conserved in RdRps across MNV and HNV norovirus variants. Conclusions In conclusion, our study suggests that the newly synthesized Co-29 may serve as a potential antiviral candidate or lead compound for future studies.
危险品化学品经营许可证（带存储）