Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide - PubMed (original) (raw)
. 2007 Apr 20;129(2):263-75.
doi: 10.1016/j.cell.2007.02.042.
Ludger Ständker, Knut Adermann, Axel Schulz, Michael Schindler, Raghavan Chinnadurai, Stefan Pöhlmann, Chawaree Chaipan, Thorsten Biet, Thomas Peters, Bernd Meyer, Dennis Wilhelm, Hong Lu, Weiguo Jing, Shibo Jiang, Wolf-Georg Forssmann, Frank Kirchhoff
Affiliations
- PMID: 17448989
- DOI: 10.1016/j.cell.2007.02.042
Free article
Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide
Jan Münch et al. Cell. 2007.
Free article
Abstract
A variety of molecules in human blood have been implicated in the inhibition of HIV-1. However, it remained elusive which circulating natural compounds are most effective in controlling viral replication in vivo. To identify natural HIV-1 inhibitors we screened a comprehensive peptide library generated from human hemofiltrate. The most potent fraction contained a 20-residue peptide, designated VIRUS-INHIBITORY PEPTIDE (VIRIP), corresponding to the C-proximal region of alpha1-antitrypsin, the most abundant circulating serine protease inhibitor. We found that VIRIP inhibits a wide variety of HIV-1 strains including those resistant to current antiretroviral drugs. Further analysis demonstrated that VIRIP blocks HIV-1 entry by interacting with the gp41 fusion peptide and showed that a few amino acid changes increase its antiretroviral potency by two orders of magnitude. Thus, as a highly specific natural inhibitor of the HIV-1 gp41 fusion peptide, VIRIP may lead to the development of another class of antiretroviral drugs.
Comment in
- Targeting the sticky fingers of HIV-1.
Blumenthal R, Dimitrov DS. Blumenthal R, et al. Cell. 2007 Apr 20;129(2):243-5. doi: 10.1016/j.cell.2007.04.005. Cell. 2007. PMID: 17448985
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