BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: HCV NS5A protein

January 7, 2016 8:00 AM UTC

In vitro studies suggest combining inhibitors of HCV NS5A protein could help treat Daklinza daclatasvir-resistant HCV infection. Screening of HCV NS5A inhibitors in a human cell-based HCV replication assay identified a compound that inhibited replication of wild-type HCV and a Daklinza-resistant HCV strain with EC50 values of 214 and 215 nM, respectively, and increased the resistant strain's sensitivity to Daklinza by over 2,600-fold compared with Daklinza alone, with EC50 values of 0.13 and 339 nM, respectively. Also in the assay, the compound increased the potency of Daklinza against 10 other resistant strains by at least 100-fold. In human liver cell-based viral elimination assays, the compound plus Daklinza and Sunvepra asunaprevir, or plus Daklinza and beclabuvir, cleared HCV replicons with potencies comparable to the combination of Daklinza, Sunvepra and beclabuvir. Next steps could include testing the compound plus Daklinza in mouse models of Daklinza-resistant HCV infection. ...