Dual Allosteric Inhibitors Jointly Modulate Protein Structure and Dynamics in the Hepatitis C Virus Polymerase.

ABSTRACT: The hepatitis C virus (HCV) infects close to 200 million people globally, resulting in a significant need for effective HCV therapies. The HCV polymerase (gene product NS5B) is a valuable target for therapeutics because of its role in replicating the viral genome. Various studies have identified inhibitors for this enzyme, including non-nucleoside inhibitors (NNIs) that bind distal to the enzyme active site. Recently, it has been shown that simultaneously challenging the enzyme with two NNIs results in enhanced inhibition relative to that observed after challenge with individual inhibitors, suggesting that employing multiple NNIs might be the basis of more effective therapeutics. Nevertheless, the molecular mechanisms responsible for this enhanced inhibition remain unclear. We employ molec

SUBMITTER: Brown JA 

PROVIDER: S-EPMC4918089 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature