ArticleJournal of the American Chemical Society2020
Structure-Guided Improvement of a Dual HPIV3/RSV Fusion Inhibitor.
Article in Journal of the American Chemical Society, 2020. 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.
- Hyperfusogenic Mutations Destabilize the Postfusion Six-Helix Bundle of the Measles Virus Fusion Glycoprotein.Biochemistry · 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
- Article
- Design and Characterization of an HRC-Derived Peptide Inhibitor of Canine Coronavirus Spike-Mediated Fusion.Pathogens (Basel, Switzerland) · 2026Article
- Enhancing the solubility of SARS-CoV-2 inhibitors to increase future prospects for clinical development.Journal of virology · 2025Article
- Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection.Antiviral research · 2025Article
- Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors.iScience · 2024Article
- Article
- Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022Article
- Antivirals targeting paramyxovirus membrane fusion.Current opinion in virology · 2021Review
- Identification of β-strand mediated protein-protein interaction inhibitors using ligand-directed fragment ligation.Chemical science · 2021Article
- Parainfluenza virus entry at the onset of infection.Advances in virus research · 2021Article
- Effects of Single α-to-β Residue Replacements on Recognition of an Extended Segment in a Viral Fusion Protein.ACS infectious diseases · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) are leading causes of lower respiratory tract infections. There are currently no vaccines or antiviral therapeutics to treat HPIV3 or RSV infections. We recently reported a peptide (VIQKI), derived from the C-terminal heptad repeat (HRC) domain of the HPIV3 fusion (F) glycoprotein that inhibits infection by both HPIV3 and RSV. The dual inhibitory activity of VIQKI is due to its unique ability to bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F, thereby preventing the native HRN-HRC interactions required for viral entry. Here we describe the structure-guided design of dual inhibitors of HPIV3 and RSV fusion with improved efficacy. We show that VIQKI derivatives possessing one (I456F) or two (I454F/I456F) phenylalanine substitutions near the N-terminus exhibit more stable assemblies with the RSV-HRN domain and enhanced antiviral efficacy against both HPIV3 and RSV infection. Cocrystal structures of the new Phe-substituted inhibitors coassembled with HPIV3 or RSV-HRN domains reveal that the I456F substitution makes intimate hydrophobic contact with the core trimers of both HPIV3 and RSV F.
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Registered trials
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.