ArticleProceedings of the National Academy of Sciences of the United States of America2022
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- In Silico Modeling of Structural Compatibility and Alignment Between Viral Class I Fusion Cores and Human TLR4/MD-2.International journal of molecular sciences · 2026Article
- Human angiotensin‑converting enzyme 2‑specific benzothiazole-based allosteric inhibitor against pan‑sarbecoviruses.Nature communications · 2026Article
- CGM23 corresponds to a pan-coronavirus lipopeptide inhibitor potently inhibiting virion fusion.iScience · 2026Article
- Recombinant Protein Nanoparticles for Dual-Stage Inhibition of SARS-CoV‑2 Infection.ACS nanoscience Au · 2026Article
- Structural and functional role of methylene linkers in self-coacervation-mediated membrane interaction and antiviral defense.Communications chemistry · 2026Article
- Tracking the protein conformational motions driving HIV-1 membrane fusion.Scientific reports · 2026Article
- Spike conformational and glycan heterogeneity associated with furin cleavage causes incomplete neutralization of SARS-CoV-2.Nature communications · 2025Article
- The F1148 hydrophobic lock: A critical determinant of SARS-CoV-2 spike protein-mediated membrane fusion via the 3H/CH cavity.PLoS pathogens · 2025Article
- Membrane-Targeting Antivirals.International journal of molecular sciences · 2025Review
- A Dual-Targeting Peptide Inhibitor Simultaneously Blocking Viral Attachment and Membrane Fusion for Broad-Spectrum Inhibition of SARS-CoV-2.International journal of molecular sciences · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Fatty acid binding protein 5 inhibitors as novel anticancer agents against metastatic castration-resistant prostate cancer.Bioorganic & medicinal chemistry · 2025Article
- Capture of fusion-intermediate conformations of SARS-CoV-2 spike requires receptor binding and cleavage at either the S1/S2 or S2' site.PLoS pathogens · 2025Article
- Enhancing the solubility of SARS-CoV-2 inhibitors to increase future prospects for clinical development.Journal of virology · 2025Article
- Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.Communications biology · 2025Article
- Structure and Function of the SARS-CoV-2 6-HB Fusion Core and Peptide-based Fusion Inhibitors: A Review.Current medicinal chemistry · 2025Review
- SARS-CoV-2 Omicron variations reveal mechanisms controlling cell entry dynamics and antibody neutralization.PLoS pathogens · 2024Article
- Review
- [3-O-β-chacotriosyl glycyrrhetinic acid derivatives as potential small-molecule SARS-CoV-2 fusion inhibitors against SARS-CoV-2 entry into host cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Ultrafast universal fabrication of configurable porous silicone-based elastomers by Joule heating chemistry.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors, which block formation of the so-called heptad repeat 1 and 2 (HR1HR2) six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. We performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit nanomolar inhibition of SARS-CoV-2 in cell-based and virus-based assays without the need for modifications such as lipidation or chemical stapling. The peptide also strongly inhibits all major SARS-CoV-2 variants to date. This extended peptide is ∼100-fold more potent than all previously published short, unmodified HR2 peptides, and it has a very long inhibition lifetime after washout in virus infection assays, suggesting that it targets a prehairpin intermediate of the SARS-CoV-2 S protein. Together, these results suggest that regions outside the HR2 helical region may offer new opportunities for potent peptide-derived therapeutics for SARS-CoV-2 and its variants, and even more distantly related viruses, and provide further support for the prehairpin intermediate of the S protein.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.