ArticleProceedings of the National Academy of Sciences of the United States of America2014
Single-chain protein mimetics of the N-terminal heptad-repeat region of gp41 with potential as anti-HIV-1 drugs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Hyperfusogenic Mutations Destabilize the Postfusion Six-Helix Bundle of the Measles Virus Fusion Glycoprotein.Biochemistry · 2026Article
- Investigating the role of a conserved hydrophobic pocket of gp41 in the anti-HIV activity of fusion inhibitors.Protein science : a publication of the Protein Society · 2026Article
- Heptad repeat 1-derived N peptide inhibitors improve broad-spectrum anti-HIV-1 activity.Current research in microbial sciences · 2025Article
- Structure and Interactions of HIV-1 gp41 CHR-NHR Reverse Hairpin Constructs Reveal Molecular Determinants of Antiviral Activity.Journal of molecular biology · 2024Article
- Helical sulfonyl-γ-AApeptides for the inhibition of HIV-1 fusion and HIF-1α signaling.RSC medicinal chemistry · 2024Review
- An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen.Emerging microbes & infections · 2023Article
- Exploring Highly Conserved Regions of SARS-CoV-2 Spike S2 Subunit as Targets for Fusion Inhibition Using Chimeric Proteins.International journal of molecular sciences · 2022Article
- Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity.International journal of biological macromolecules · 2022Article
- Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up New Ways of Inhibiting HIV-1 Fusion.International journal of molecular sciences · 2022Article
- Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus.Emerging microbes & infections · 2021Article
- Article
- The CH1α domain of mucosal gp41 IgA contributes to antibody specificity and antiviral functions in HIV-1 highly exposed Sero-Negative individuals.PLoS pathogens · 2020Article
- Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors.Viruses · 2020Article
- The Tryptophan-Rich Motif of HIV-1 gp41 Can Interact with the N-Terminal Deep Pocket Site: New Insights into the Structure and Function of gp41 and Its Inhibitors.Journal of virology · 2019Article
- De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery.Journal of medicinal chemistry · 2018Article
- Exceptional potency and structural basis of a T1249-derived lipopeptide fusion inhibitor against HIV-1, HIV-2, and simian immunodeficiency virus.The Journal of biological chemistry · 2018Article
- Mechanism of HIV-1 Resistance to an Electronically Constrained α-Helical Peptide Membrane Fusion Inhibitor.Journal of virology · 2018Article
- Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition.Journal of virology · 2017Article
- Site-specific Isopeptide Bridge Tethering of Chimeric gp41 N-terminal Heptad Repeat Helical Trimers for the Treatment of HIV-1 Infection.Scientific reports · 2016Article
- Designing helical peptide inhibitors of protein-protein interactions.Current opinion in structural biology · 2016Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During HIV-1 fusion to the host cell membrane, the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) of the envelope subunit gp41 become transiently exposed and accessible to fusion inhibitors or Abs. In this process, the NHR region adopts a trimeric coiled-coil conformation that can be a target for therapeutic intervention. Here, we present an approach to rationally design single-chain protein constructs that mimic the NHR coiled-coil surface. The proteins were built by connecting with short loops two parallel NHR helices and an antiparallel one with the inverse sequence followed by engineering of stabilizing interactions. The constructs were expressed in Escherichia coli, purified with high yield, and folded as highly stable helical coiled coils. The crystal structure of one of the constructs confirmed the predicted fold and its ability to accurately mimic an exposed gp41 NHR surface. These single-chain proteins bound to synthetic CHR peptides with very high affinity, and furthermore, they showed broad inhibitory activity of HIV-1 fusion on various pseudoviruses and primary isolates.
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