ArticleNature microbiology2020
Orally efficacious broad-spectrum allosteric inhibitor of paramyxovirus polymerase.
Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- Antiviral GHP-88310 blocks contact-mediated and airborne transmission in a ferret model of measles-like disease.Nature microbiology · 2026Article
- Identification and characterization of novel chikungunya virus polymerase inhibitors.Journal of virology · 2026Article
- Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models.Science advances · 2026Article
- Structural insights into measles virus RNA synthesis regulation and pan-paramyxoviral polymerase inhibition by ERDRP-0519.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- De novo recovery of Ghana virus, an African bat Henipavirus, reveals differential tropism and attenuated pathogenicity compared to Nipah virus.Cell reports · 2026Article
- Impact of mutations affecting 4'-fluorouridine susceptibility on fitness and treatment outcomes for Venezuelan equine encephalitis virus.Journal of virology · 2026Article
- Protection against lethal canine distemper virus infection by a dual epitope-targeting synthetic antibody.Nature communications · 2026Article
- Review
- Allosteric pockets in the measles and Nipah virus polymerases: Mechanobiological insights and AI-driven drug discovery opportunities.Mechanobiology in medicine · 2025Article
- Status of advanced respiratory syncytial virus antiviral therapeutics 2025.Current opinion in virology · 2025Review
- Applications of human lung organoids to human respiratory virus research: advances, limitations and future directions.Infection · 2025Review
- Applications and research trends in organoid based infectious disease models.Scientific reports · 2025Review
- Lung organoids: a new frontier in neonatology and paediatric respiratory medicine.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Article
- Serial Adaptation of Viruses for Reduced Susceptibility Profiling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cryo-EM structure of Nipah virus L-P polymerase complex.Nature communications · 2024Article
- Tetracistronic minigenomes elucidate a functional promoter for Ghana virus and unveils Cedar virus replicase promiscuity for all henipaviruses.Journal of virology · 2024Article
- Structural basis of paramyxo- and pneumovirus polymerase inhibition by non-nucleoside small-molecule antivirals.Antimicrobial agents and chemotherapy · 2024Review
- Tetracistronic Minigenomes Elucidate a Functional Promoter for Ghana Virus and Unveils Cedar Virus Replicase Promiscuity for all Henipaviruses.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Paramyxoviruses such as human parainfluenza virus type-3 (HPIV3) and measles virus (MeV) are a substantial health threat. In a high-throughput screen for inhibitors of HPIV3 (a major cause of acute respiratory infection), we identified GHP-88309-a non-nucleoside inhibitor of viral polymerase activity that possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses (that is, HPIV1 and HPIV3) and morbilliviruses (that is, MeV). Resistance profiles of distinct target viruses overlapped spatially, revealing a conserved binding site in the central cavity of the viral polymerase (L) protein that was validated by photoaffinity labelling-based target mapping. Mechanistic characterization through viral RNA profiling and in vitro MeV polymerase assays identified a block in the initiation phase of the viral polymerase. GHP-88309 showed nanomolar potency against HPIV3 isolates in well-differentiated human airway organoid cultures, was well tolerated (selectivity index > 7,111) and orally bioavailable, and provided complete protection against lethal infection in a Sendai virus mouse surrogate model of human HPIV3 disease when administered therapeutically 48 h after infection. Recoverees had acquired robust immunoprotection against reinfection, and viral resistance coincided with severe attenuation. This study provides proof of the feasibility of a well-behaved broad-spectrum allosteric antiviral and describes a chemotype with high therapeutic potential that addresses major obstacles of anti-paramyxovirus drug development.
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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.