Understanding the molecular targets for new therapeutical agents in hepatitis c infection.
Improved understanding of the HCV viral life cycle has led to the identification of numerous potential molecular targets for the development of new drugs. Direct acting antivirals -DAAs specifically target a viral encoded protein: the NS3-4A protease, involved in the posttranslational viral protein processing; the NS5B encoded viral polymerase, that conducts the nucleic acid replication and the NS5A encoded phosphoprotein, that participates in both replication and virus assembly. Host-targeted agents, both directed to the early steps of viral replication (receptors and coreceptors antagonists) or to the development of a functional viral replication complex (host cyclophilins) are also developed, to strengthen the antiviral efficacy of these drugs. The newly approved NS3-4A protease inhibitors (telaprevir and boceprevir), administered in combination with pegylated interferon and ribavirin for patients with HCV genotype I infection, determined a significant enhancement in the sustained virologic response rates (towards 66-75% in treatment-naive patients and 59-66% in treatment-experienced ones). Improved antiviral efficacy was shown in clinical trials by second generation protease inhibitors, while valuable alternatives are represented by nucleoside/nucleotide analogues and non-nucleoside inhibitors directed to the HCV RNA-dependent RNA polymerase, as well as by NS5A inhibitors (both direct acting or directed to the host cofactors). More recently, combinations of different drugs are tested as a potential cure for chronic hepatitis C.
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Codruţa
C
Vagu
Camelia
C
Sultana
Simona
S
Ruţă
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D014764:Viral Proteins