Abstract: Methods for determining the susceptibility of a hepatitis C virus (HCV) in a patient to anti-viral agents, particularly cyclophilin inhibitors such as cyclosporine A, are disclosed. The methods include determining the amino acid sequence within a region of the HCV NS5A protein and comparing the viral amino acid sequence to that of a reference strain, wherein the existence of at least one variant/mutation in the viral genome is indicative that the virus is more or less susceptible to anti-viral agents. Also disclosed are isolated polynucleotide molecules, replicons, and kits that can be used to assay the susceptibility of hepatitis HCV in a patient to anti-viral agents.