id author title date pages extension mime words sentences flesch summary cache txt cord-002990-7flusgus Kitano, Mitsutaka Selection and Characterization of Rupintrivir-Resistant Norwalk Virus Replicon Cells In Vitro 2018-04-26 .txt text/plain 7080 313 50 The application of a cell-based fluorescence resonance energy transfer (FRET) assay for protease activity demonstrated that these substitutions were involved in the enhanced resistance to rupintrivir. Furthermore, we validated the effect of these mutations using reverse genetics in murine norovirus (MNV), demonstrating that a recombinant MNV strain with a single I109V substitution in the protease also showed reduced susceptibility to rupintrivir. In the present study, we isolated replicon cells with reduced susceptibility to rupintrivir after several passages in the presence of rupintrivir and identified two amino acid substitutions of alanine 105 to valine (A105V) and isoleucine 109 to valine (I109V) in the viral protease. To confirm the previously reported inhibitory effects of rupintrivir on human norovirus replication (10), we generated a human gastric adenocarcinoma cell line, HGT-NV, which stably maintained a Norwalk virus replicon encoding the neomycin resistance gene in place of the major capsid protein. ./cache/cord-002990-7flusgus.txt ./txt/cord-002990-7flusgus.txt