NS5B RNA Dependent RNA Polymerase Inhibitors: The Promising Approach to Treat Hepatitis C Virus Infections

摘要

Hepatitis C virus (HCV), a causative agent for non-A and non-B hepatitis, has infected approximately 3% of nworld’s population. The current treatment option of ribavirin in combination with pegylated interferon possesses lower nsustained virological response rates, and has serious disadvantages. Unfortunately, no prophylactic vaccine has been ap-nproved yet. Therefore, there is an unmet clinical need for more effective and safe anti-HCV drugs. HCV NS5B RNA de-npendent RNA polymerase is currently pursued as the most popular target to develop safe anti-HCV agents, as it is not ex-npressed in uninfected cells. More than 25 pharmaceutical companies and some research groups have developed ~50 struc-nturally diverse scaffolds to inhibit NS5B. Here we provide comprehensive account of the drug development process of nthese scaffolds. NS5B polymerase inhibitors have been broadly classified in nucleoside and non nucleoside inhibitors and nare sub classified according to their mechanism of action and structural diversities. With some additional considerations nabout the inhibitor bound NS5B enzyme X-ray crystal structure information and pharmacological aspects of the inhibitors, nthis review summarizes the lead identification, structure activity relationship (SAR) studies leading to the most potent nNS5B inhibitors with subgenomic replicon activity