Title:Peptide-based Fusion Inhibitors for Preventing the Six-helix Bundle Formation of Class I Fusion Proteins: HIV and Beyond
Volume: 19
Issue: 6
Author(s): Ajit Monteiro, Karl O. A. Yu and Mark D. Hicar*
Affiliation:
- Department of Pediatrics, University at Buffalo, Buffalo, New York, 14260,United States
Keywords:
HIV, T20, enfuvirtide, gp41, fusion, SARS, Coronaviruses.
Abstract: A number of different viral families have developed convergent methods to infect cells.
Class I fusion proteins are commonly used by members of Arenaviridae, Coronaviridae, Filovirdae,
Orthomyxoviridae, Paramyxoviridae, and Retroviridae. Class I viral fusion proteins are
trimers that are involved in recognizing the cellular receptor, with a region that is responsible for
fusing the viral and target cell membranes. During the fusion process, the fusion region folds into a
six-helix bundle (6 HB) which approximates the two membranes leading to fusion. For Human Immunodeficiency
Virus (HIV), the gp41 subunit is responsible for the formation of this 6 HB. The
fusion inhibitor drug enfuvirtide, or T20, is the only US Food and Drug Administration and European
Medicines Agency approved drug which targets this crucial step and has been widely used in
combination regimens for the treatment of HIV since March 2003. In this review, we describe the
current state of peptide-based fusion inhibitors in the treatment of HIV, and review how the field of
HIV research is driving advances in the development of similar therapeutics in other viral systems,
including the Severe Acute Respiratory Syndrome (SARS) coronaviruses.