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. 2025 Nov;46(11):3009-3021.
doi: 10.1038/s41401-025-01535-5. Epub 2025 Jun 5.

The conformational epitope of a gp41-specific mucosal protective IgA binds to the HIV-1 envelope and neutralizes infection

Inès Sahnoune  1   2 , Andréa Cottignies-Calamarte  1   2 , Annouk Dauvilliers  1   2 , Kingsley Essemiah  1   2   3 , Tahar Bouceba  4 , Christophe Piesse  4 , Daniela Tudor  1   2 , Morgane Bomsel  5   6
Affiliations

The conformational epitope of a gp41-specific mucosal protective IgA binds to the HIV-1 envelope and neutralizes infection

Inès Sahnoune et al. Acta Pharmacol Sin. 2025 Nov.

Abstract

HIV-1 envelope conformational changes necessary for viral infection make the gp41 subunit a key target for antiviral drugs. Using reverse vaccinology applied to a mucosal HIV-1 neutralizing IgA, we identified P7, a 12 amino-acid peptide at the interface of the N and C-helices of gp41. We now show that P7 interacts with the trimeric HIV-1 envelope cross-clade with a nanomolar affinity, captures gp41 in a 6-Helix Bundle conformation, and binds to infected cells and free virus. Functionally, P7 neutralizes HIV infection cross-clade and inhibits cell-to-cell viral transfer. Adding a lipid tail to P7 (Lipo-P7) improved neutralization of primary CD4+ T cells by Transmitted / Founder clade B and primary clades A and C viruses. Lipo-P7 also neutralized a T20-resistant virus harboring gp41 G36D, V38M mutations. Altogether, P7 appears as a promising cross-clade HIV-1 antiviral peptide that could also induce protective mucosal IgA levels to prevent sexual HIV infection.

Keywords: HIV envelop protein gp41; anti-HIV drugs; conformational epitope; mucosal IgA.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Chen B. Molecular mechanism of HIV-1 entry. Trends Microbiol. 2019;27:878–91. - PMC - PubMed
    1. Ye L, Wen Z, Dong K, Wang X, Bu Z, Zhang H, et al. Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines. PLoS One. 2011;6:e14813. - PMC - PubMed
    1. Root MJ, Steger HK. HIV-1 gp41 as a target for viral entry inhibition. Curr Pharm Des. 2004;10:1805–25. - PubMed
    1. Chan DC, Kim PS. HIV entry and its inhibition. Cell. 1998;93:681–4. - PubMed
    1. He Y. Synthesized peptide inhibitors of HIV-1 gp41-dependent membrane fusion. Curr Pharm Des. 2013;19:1800–9. - PubMed

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