Publication
Hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) is a complex composed of NS3 and its cofactor NS4A. It harbours serine protease as well as NTPase/RNA helicase activities and is essential for viral polyprotein processing, RNA replication and virion formation. Specific inhibitors of the NS3-4A protease significantly improve sustained virological response rates in patients with chronic hepatitis C when combined with pegylated interferon-α and ribavirin. The NS3-4A protease can also target selected cellular proteins, thereby blocking innate immune pathways and modulating growth factor signalling. Hence, NS3-4A is not only an essential component of the viral replication complex and prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. This review provides a concise update on the biochemical and structural aspects of NS3-4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3-4A protease inhibitors.
Jacques Fellay, Bruno Emanuel Ferreira De Sousa Correia, Andreas Scheck, Olivier Noël Marie Naret, Arne Schneuing, David Gfeller, Thomas Junier, Zhi Ming Xu, Dylan Lawless, Sina Rüeger
Didier Trono, Priscilla Turelli, Sandra Eloise Kjeldsen, Evaristo Jose Planet Letschert, Filipe Amândio Brandão Sanches Vong Martins, Florian Huber, Cyril David Son-Tuyên Pulver, Olga Marie Louise Rosspopoff, Romain Forey, Joana Carlevaro Fita
Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Francisco De Magalhães Sarmento R De Mesquita