ArticleProceedings of the National Academy of Sciences of the United States of America2023
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 11 citations in OpenAlex.
- mRNA Vaccines Targeting the Conserved SARS-CoV-2 Fusion Machinery Elicit Cross-Variant and Robust Immunity.Vaccines · 2026Article
- 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
- Genomic surveillance of SARS-CoV-2 variants in hospitalized patients: a cohort study from the metropolitan area of valle de Aburrá, ColombiaBiomedica : revista del Instituto Nacional de Salud · 2026Article
- From single-sequences to evolutionary trajectories: protein language models capture the evolutionary potential of SARS-CoV-2.Nature communications · 2026Article
- Mutation and ACE2-induced allosteric network rewiring in Delta and Omicron SARS-CoV-2 spike proteins.Biophysical journal · 2026Article
- Mutation and ACE2-induced Allosteric Network Rewiring in Delta and Omicron SARS-CoV-2 Spike Proteins.bioRxiv : the preprint server for biology · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- The Compensatory Effect of S375F on S371F Is Vital for Maintaining the Infectivity of SARS-CoV-2 Omicron Variants.Journal of medical virology · 2025Article
- Computational optimization of a pan-coronavirus fusion inhibitory peptide targeting spike's heptapeptide repeat region.Biosafety and health · 2025Article
- Structure and Function of the SARS-CoV-2 6-HB Fusion Core and Peptide-based Fusion Inhibitors: A Review.Current medicinal chemistry · 2025Review
- Article
- Characterization of the viral genome of Omicron variants of SARS-CoV-2 circulating in Tripura, a remote frontier state in Northeastern India.Molecular biology reports · 2024Article
- Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion.RSC chemical biology · 2024Article
- Viral Membrane Fusion: A Dance Between Proteins and Lipids.Annual review of virology · 2023Review
- Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide inhibitors based on the Wuhan strain sequence are less efficacious. Here, we report an Omicron-specific peptide inhibitor designed based on the structure of the Omicron HR1HR2 postfusion bundle. Specifically, we inserted an additional residue in HR2 near the Omicron HR1 K969 residue to better accommodate the N969K mutation and relieve the distortion in the structure of the HR1HR2 postfusion bundle it introduced. The designed inhibitor recovers the loss of inhibition activity of the original longHR2_42 peptide with the Wuhan strain sequence against the Omicron variant in both a cell-cell fusion assay and a vesicular stomatitis virus (VSV)-SARS-CoV-2 chimera infection assay, suggesting that a similar approach could be used to combat future variants. From a mechanistic perspective, our work suggests the interactions in the extended region of HR2 may mediate the initial landing of HR2 onto HR1 during the transition of the S protein from the prehairpin intermediate to the postfusion state.
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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.