ArticleProceedings of the National Academy of Sciences of the United States of America2010
Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus.Antimicrobial agents and chemotherapy · 2020Trial
- Catching our breath: development of interventions and therapies for respiratory syncytial virus.Microbiology and molecular biology reviews : MMBR · 2026Review
- Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC.Journal of virology · 2026Article
- Review
- A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses.Nature communications · 2025Article
- Review
- Advances in development of antiviral strategies against respiratory syncytial virus.Acta pharmaceutica Sinica. B · 2025Review
- Ebola and Marburg virus VP35 coiled-coil validated as antiviral target by tripartite split-GFP complementation.iScience · 2022Article
- Review
- Small-Molecule Inhibition of Viral Fusion Glycoproteins.Annual review of virology · 2021Review
- Mechanism of Cross-Resistance to Fusion Inhibitors Conferred by the K394R Mutation in Respiratory Syncytial Virus Fusion Protein.Journal of virology · 2021Article
- Discovery of a Novel Respiratory Syncytial Virus Replication Inhibitor.Antimicrobial agents and chemotherapy · 2021Article
- Pharmacological Characterization of TP0591816, a Novel Macrocyclic Respiratory Syncytial Virus Fusion Inhibitor with Antiviral Activity against F Protein Mutants.Antimicrobial agents and chemotherapy · 2020Article
- Inhibitory Effect of PIK-24 on Respiratory Syncytial Virus Entry by Blocking Phosphatidylinositol-3 Kinase Signaling.Antimicrobial agents and chemotherapy · 2020Article
- Review
- Respiratory syncytial virus entry and how to block it.Nature reviews. Microbiology · 2019Review
- Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Respiratory Syncytial Virus Infects Primary Neonatal and Adult Natural Killer Cells and Affects Their Antiviral Effector Function.The Journal of infectious diseases · 2019Article
- Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.Nature communications · 2017Article
- A Short Double-Stapled Peptide Inhibits Respiratory Syncytial Virus Entry and Spreading.Antimicrobial agents and chemotherapy · 2017Article
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14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Six-helix bundle (6HB) formation is an essential step for many viruses that rely on a class I fusion protein to enter a target cell and initiate replication. Because the binding modes of small molecule inhibitors of 6HB formation are largely unknown, precisely how they disrupt 6HB formation remains unclear, and structure-based design of improved inhibitors is thus seriously hampered. Here we present the high resolution crystal structure of TMC353121, a potent inhibitor of respiratory syncytial virus (RSV), bound at a hydrophobic pocket of the 6HB formed by amino acid residues from both HR1 and HR2 heptad-repeats. Binding of TMC353121 stabilizes the interaction of HR1 and HR2 in an alternate conformation of the 6HB, in which direct binding interactions are formed between TMC353121 and both HR1 and HR2. Rather than completely preventing 6HB formation, our data indicate that TMC353121 inhibits fusion by causing a local disturbance of the natural 6HB conformation.
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