Direct-acting and host-targeting HCV inhibitors: current and future directions

The inclusion of NS3 protease inhibitors to the interferon-containing standard of care improved sustained viral response rates in hepatitis C virus (HCV) infected patients. However, there is still an unmet medical need as this drug regimen is poorly tolerated and lacks efficacy, especially in difficult-to-treat patients. Intense drug discovery and development efforts have focused on direct-acting antivirals (DAA) that target NS3 protease, NS5B polymerase and the NS5A protein. DAA combinations are currently assessed in clinical trials. Alternative antivirals have emerged that target host machineries co-opted by HCV. Finally, continuous and better understanding of HCV biology allows speculating on the value of novel classes of DAA required in future personalized all-oral interferon-free combination therapy and for supporting global disease eradication.

► Direct-acting antivirals (DAA) are currently challenged in HCV infected patients. ► Cellular machineries co-opted by HCV represent promising host targeting antivirals (HTA). ► Successful HCV therapies are achieved with all-oral IFN free drug combination. ► Future therapy will rely on individualized regimen of various classes of DAA and/or HTA.