ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors.
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 60 papers.
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Who cites it
60 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
- Antiviral activity of the non-steroidal anti-inflammatory drug indomethacin against respiratory syncytial virus.Virus research · 2026Article
- Catching our breath: development of interventions and therapies for respiratory syncytial virus.Microbiology and molecular biology reviews : MMBR · 2026Review
- Expanded Genomic Surveillance and Seasonal Comparisons of Human Respiratory Syncytial Virus Infections in Minnesota, USA, 2023-2025.Influenza and other respiratory viruses · 2026Article
- Respiratory syncytial virus mRNA vaccine-induced immunity and protection against subgroups A and B in mice.ImmunoHorizons · 2026Article
- 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
- Status of advanced respiratory syncytial virus antiviral therapeutics 2025.Current opinion in virology · 2025Review
- Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys.Nature communications · 2025Article
- Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.Journal of virology · 2024Article
- Ethanolic Extract fromPreventive nutrition and food science · 2024Article
- Article
- Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.Signal transduction and targeted therapy · 2024Article
- Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor.Nature communications · 2024Article
- Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets.Nature communications · 2024Article
- Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins.Frontiers in immunology · 2024Article
- Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance.Virus evolution · 2024Article
- Modeling structure-activity relationships with machine learning to identify GSK3-targeted small molecules as potential COVID-19 therapeutics.Frontiers in endocrinology · 2023Article
- Respiratory Syncytial Virus Two-Step Infection Screen Reveals Inhibitors of Early and Late Life Cycle Stages.Antimicrobial agents and chemotherapy · 2022Article
- Orally efficacious lead of the AVG inhibitor series targeting a dynamic interface in the respiratory syncytial virus polymerase.Science advances · 2022Article
- Protein and Peptide Substances in the Treatment of Respiratory Syncytial Infection: Current State.Molecules (Basel, Switzerland) · 2022Review
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Authors and funding
6 authors.
Funding
Abstract
Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A structural and biochemical assessment of the mechanism of unique, broad RSV cross-resistance against structurally distinct entry inhibitors demonstrated that individual escape hotspots are located in immediate physical proximity in the metastable conformation of RSV F and that the resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV entry kinetics. One resistant RSV recombinant remained fully pathogenic in a mouse model of RSV infection. By identifying molecular determinants governing the RSV entry machinery, this study spotlights a molecular mechanism of broad RSV resistance against entry inhibition that may affect the impact of diverse viral entry inhibitors presently considered for clinical use and outlines a proactive design for future RSV drug discovery campaigns.
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