Development of antiviral drugs for the treatment of hepatitis C at an accelerating pace.

Abstract

Anno 2015, the race for developing the ideal therapy, or what is now called "cure," for hepatitis C virus infection has continued unabatedly. The targets (NS3/4A protease, NS5A protein, and NS5B polymerase) have remained the same, and the number of compounds [direct-acting antivirals (DAAs)] interacting with these targets has continued to increase. Whereas pan-genotypic activity has remained a mandatory requirement, the problem of virus drug resistance has become less crucial. The need for combining DAAs acting at different sites has remained compelling, with the drugs used for combinations emanating from the same pharmaceutical company, that is, Gilead (sofosbuvir and ledipasvir) (Gilead Sciences, Foster City, CA, USA) (AbbVie, North Chicago, IL, USA), AbbVie (ABT/r, ombitasvir, and dasabuvir), and BMS (Bristol-Myers Squibb), (New York City, NY, USA) (asunaprevir and daclatasvir) among the leading contenders. At stake is the definitive cure of HCV infection [as reflected by a sustained viral response (SVR) after 12 weeks of treatment]. This SVR is expected to reduce cirrhosis and hepatocellular carcinoma, two complications inherently linked to HCV infection. Unlike hepatitis B virus and human immunodeficiency virus, HCV infection can be definitely and permanently cured by antiviral therapy because HCV has no long-term reservoir in the body. Peginterferon combined with ribavirin and even the first-wave protease inhibitors telaprevir and boceprevir now belong to the milestones that had an important, although historical, role in the final conquest of hepatitis C.