SARS-CoV-2 NSP14 inhibitor C10 is a potent, selective non-nucleoside inhibitor of SARS-CoV-2 nonstructural protein 14 (NSP14) with IC50 of 0.34 uM, exhibits potent antiviral activity and reverses NSP14-driven host modulation.
C10 targets NSP14 S-adenosylmethionine (SAM)-binding pocket.
C10 inhibits original SARS-CoV-2 and Delta variant with EC50 values of 0.31 µM and 0.50 µM, respectively, and inhibits the Omicron variant reached up to 64 nM with low cytotoxicity (CC50 > 100 uM).
C10 inhibits HCoV-OC43 infection in A549-ACE2 cells with an EC50 value of 4.36 µM, while the inhibition of HCoV-229E infection is negligible.
C10 inhibits SARS-CoV-2 at the replication stage, suppresses viral translation and exhibits immunostimulatory effect.
C10 reverses NSP14-mediated host transcriptome modulation.
C10 (70 mg/kg, i,p., 5% dimethyl sulfoxide and 95% cyclodextrin solution) demonstrates antiviral efficacy in K18-hACE2 transgenic mouse model.