Discovery of a Novel Class of Norovirus Inhibitors with High Barrier of Resistance.

ABSTRACT: Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting in ~219,000 deaths annually and a societal cost of ~USD60 billion. There are no antivirals or vaccines available to treat and/or prevent HuNoV. In this study, we performed a large-scale phenotypical antiviral screening using the mouse norovirus (MNV), which included ~1000 drug-like small molecules from the Drug Design and Synthesis Centre (Sapienza University, Rome). Compound 3-((3,5-dimethylphenyl)sulfonyl)-5-chloroindole-N-(phenylmethanol-4-yl)-2.carboxamide (compound 1) was identified as an inhibitor of MNV replication with an EC₅₀ of 0.5 ± 0.1 µM. A series of 10 analogs were synthesized of which compound 6 showed an improved potency/selectivity (EC₅₀ 0.2 ± 0.1 µM)

SUBMITTER: Van Dycke J 

PROVIDER: S-EPMC8537218 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature