HCV E2 core structures and mAbs: Something is still missing

Matteo Castelli, Nicola Clementi, Giuseppe A. Sautto, Jennifer Pfaff, Kristen M. Kahle, Trevor Barnes, Benjamin J. Doranz, Matteo Dal Peraro, Massimo Clementi, Roberto Burioni, Nicasio Mancini

Research output: Contribution to journalArticle

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 Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity.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.

Original languageEnglish
Pages (from-to)1964-1970
Number of pages7
JournalDrug Discovery Today
Volume19
Issue number12
DOIs
Publication statusPublished - Nov 17 2014

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

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    Castelli, M., Clementi, N., Sautto, G. A., Pfaff, J., Kahle, K. M., Barnes, T., Doranz, B. J., Dal Peraro, M., Clementi, M., Burioni, R., & Mancini, N. (2014). HCV E2 core structures and mAbs: Something is still missing. Drug Discovery Today, 19(12), 1964-1970. https://doi.org/10.1016/j.drudis.2014.08.011