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Drug Discov Today. 2014 Dec;19(12):1964-70. doi: 10.1016/j.drudis.2014.08.011. Epub 2014 Aug 27.

HCV E2 core structures and mAbs: something is still missing.

Author information

1
Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
2
Integral Molecular, Philadelphia, USA.
3
Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
4
Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy. Electronic address: mancini.nicasio@hsr.it.

Abstract

The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studies, the E2 overall structure is still unknown and, most importantly, several biochemical and functional studies are in disagreement with E2c structures. Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity. A modeling strategy aiming at recapitulating the available structural and functional studies of E2 will also be proposed.

PMID:
25172800
PMCID:
PMC4706463
DOI:
10.1016/j.drudis.2014.08.011
[Indexed for MEDLINE]
Free PMC Article

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