Helicases as antiviral drug targets.

Abstract

Helicases catalytically unwind duplex DNA or RNA using energy derived from the hydrolysis of nucleoside triphosphates and are attractive drug targets because they are required for viral replication. This review discusses methods for helicase identification, classification and analysis, and presents an overview of helicases that are necessary for the replication of human pathogenic viruses. Newly developed methods to analyze helicases, coupled with recently determined atomic structures, have led to a better understanding of their mechanisms of action. The majority of this research has concentrated on enzymes encoded by the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Helicase inhibitors that target the HSV helicase-primase complex comprised of the UL5, UL8 and UL52 proteins have recently been shown to effectively control HSV infection in animal models. In addition, several groups have reported structures of the HCV NS3 helicase at atomic resolutions, and mechanistic studies have uncovered characteristics that distinguish the HCV helicase from related cellular proteins. These new developments should eventually lead to new antiviral medications.