Grant: Operating Grant

The hepatitis C virus (HCV) is a major human pathogen. Infection with the virus can cause severe liver disease, including cancer. Unfortunately, by far not everyone benefits from available therapies. Although several new antiviral agents have been developed, many of these drugs lose their activity over time. The virus changes rapidly and certain genetic variants can survive in the presence of literally any given drug. Here we hypothesize that a complex interplay between the frequency with which these mutations emerge and the efficiency with which the resistant viruses can replicate can determine success or failure of a given antiviral drug. We propose to employ a combination of biochemical experiments and cell-based assays to tackle this problem. Success in the proposed research will likely contribute to the design of drugs and drug combinations that are associated with a high barrier to the development of resistance.