A REVIEW ON ANTI-HCV AGENTS TARGETING ACTIVE SITE AND ALLOSTERIC SITES OF NON-STRUCTURAL PROTEIN 5B [NS5B]
DOI:
https://doi.org/10.22159/ijpps.2016v8i11.13965Keywords:
Hepatitis C virus, NS5B, Inhibitors, Structure-Activity relationships, Genotypic variance, Allosteric site, Active siteAbstract
Hepatitis C, a chronic disease affecting the global population significantly is caused majorly by Hepatitis C virus [HCV]. Among the several druggable targets explored for Hepatitis C, the viral protein, non-structural protein 5B [NS5B] is the target of choice for researchers as it is the key enzyme in the HCV replication and its active site is conserved among all genotypes. In the recent years the landscape of Hepatitis C therapies, have evolved from Peg-Interferon [PEG-INF]/Ribavirin, to directly acting anti-virus along with PEG-INF and finally, INF free regimens with greater than 90% sustained virological response [SVR]. The launch of Sofosbuvir, a nucleotide inhibitor of NS5B marks the major paradigm in hepatitis C research. Sofosbuvir exhibits, pan-genotypic activity, low barrier to resistance, highly effective and safe. However, the high prices of these medications limit their universal access. This review will focus on progress towards the discovery and development of NS5B inhibitors targeting allosteric sites and active site, covering the chemical class and structure-activity relationships.
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