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278 : 19071916 Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai L-H

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Telaprevir as monotherapy had minimal activity against HCV-3, as noted by a mild decrease in HCV RNA levels (-0.54 log10 IU/L at day 15),[70] while boceprevir has been found to be slightly more active than telaprevir against HCV-3 in cell-based assays, and to decrease HCV RNA levels comparable to those observed with the same dose in HCV-1 treatment-experienced patients in a phase 1 study.[71] As we have advanced in HCV therapy, even second wave protease inhibitors simeprevir, asunaprevir, faldaprevir and danoprevir have demonstrated limited activity against HCV-3.[72] Advances in therapy The main mechanism of action of most DAAs is the inhibition of an enzyme (protease or polymerase),[73] although some inhibit the assembly of the replication complex (NS5A inhibitors) or target the host factors that the virus uses (cyclophilin inhibitors)[74] (Table 1)