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