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Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide
Open accessAbstract
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.
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Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60
Hallenberger, S., Bosch, V., Angliker, H., Shaw, E., Klenk, H.-D., & Garten, W. (1992) · Nature · doi:10.1038/360358a0 · Cited by 582
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Yu, P., Lübben, W., Slomka, H., Gebler, J., Konert, M., Cai, C., Neubrandt, L., Prazeres da Costa, O., Paul, S., Dehnert, S., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.07.018 · Cited by 192
Metadata
- Authors
- Münch, J., Ständker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pöhlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., & Kirchhoff, F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 129
- Issue
- 2
- Pages
- 263-275
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2026361605
- Cited by
- 261
- References
- 2
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Münch, J., Ständker, L., Adermann, K., Schulz, A., Schindler, M., Chinnadurai, R., Pöhlmann, S., Chaipan, C., Biet, T., Peters, T., Meyer, B., Wilhelm, D., Lu, H., Jing, W., Jiang, S., Forssmann, W.-G., & Kirchhoff, F. (2007). Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide. Cell. https://doi.org/10.1016/j.cell.2007.02.042
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