rupintrivir and Caliciviridae-Infections

Noroviruses are members of the family Caliciviridae. Norovirus infections are a global health burden that impacts >20 million individuals annually in the U.S. alone. Noroviruses are associated with high morbidity among vulnerable populations, particularly immunocompromised patients. This perspective highlights recent developments related to the discovery and development of norovirus-specific small-molecule therapeutics as well as recent advances in our understanding of norovirus biology and pathogenesis. Most of the work in this area is at the early discovery stage and has been primarily focused on inhibitors of norovirus 3C-like protease and RNA dependent RNA polymerase. However, recent discoveries emanating from basic studies in norovirus research have resulted in the identification of new host-related drug targets that can be exploited. A repurposed compound has been advanced to human clinical studies.

Topics: Animals; Antiviral Agents; Caliciviridae Infections; Cysteine Proteinase Inhibitors; Gastroenteritis; Genes, Viral; Humans; Norovirus; RNA-Dependent RNA Polymerase; Virus Internalization

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to the protease inhibitor rupintrivir. The early hit compound

Topics: Animals; Caliciviridae Infections; Cell Line; Cytopathogenic Effect, Viral; Drug Resistance, Viral; Isoxazoles; Microbial Sensitivity Tests; Molecular Docking Simulation; Mutation; Norovirus; Peptide Hydrolases; Phenylalanine; Pyrrolidinones; Replicon; RNA, Viral; Small Molecule Libraries; Valine; Viral Protease Inhibitors; Virus Replication; Zebrafish