targeting hcv entry for development of therapeutics针对丙肝病毒条目疗法的发展.pdf

Viruses 2010, 2, 1718-1733; doi:10.3390/v2081718 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Targeting HCV Entry For Development of Therapeutics Flossie Wong-Staal *, Andrew J. Syder and Jeffrey F. McKelvy iTherX Pharmaceuticals, In., P.O. Box 910530, CA 910530, USA; E-Mails: dsyder@ (A.J.S.); jmckelvy@ (J.F.M.) * Author to whom correspondence should be addressed; E-Mail: fwongstaal@; Tel.: +1-858-824-1114; Fax: +1-858-824-1112. Received: 28 June 2010; in revised form: 5 August 2010 / Accepted: 16 August 2010 / Published: 18 August 2010 Abstract: Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL) with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI), CD81, Claudin 1 (CLDN1) and Occludin (OCLN). The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one st