ArticleJournal of virology2016
A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.
Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The trial behind it
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Towards broader-spectrum direct-acting antivirals against RNA viruses.Nature reviews. Microbiology · 2026Review
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.PLoS pathogens · 2026Article
- Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.bioRxiv : the preprint server for biology · 2025Article
- Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17-21, 2025.Antiviral research · 2025Article
- Modes of action of a small molecule antiviral compound targeting yellow fever virus NS4B protein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- Flavivirus NS4B proteins do not form homodimers: discrepancies with an AlphaFold-based oligomeric model.Computational and structural biotechnology journal · 2025Article
- Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20-24, 2024, organized by the International Society for Antiviral Research.Antiviral research · 2024Article
- Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation.Nature communications · 2024Article
- Multiplexed multicolor antiviral assay amenable for high-throughput research.Nature communications · 2024Article
- 1-Sulfonyl-3-amino-1ACS omega · 2023Article
- Flavivirus nonstructural proteins and replication complexes as antiviral drug targets.Current opinion in virology · 2023Review
- Synthetic aspects of 1,4- and 1,5-benzodiazepines usingRSC advances · 2023Review
- Rifapentine is an entry and replication inhibitor against yellow fever virus both in vitro and in vivo.Emerging microbes & infections · 2022Article
- Flavivirus NS4B protein: Structure, function, and antiviral discovery.Antiviral research · 2022Review
- Bis(Benzofuran-1,3-International journal of molecular sciences · 2022Article
- A yellow fever virus NS4B inhibitor not only suppresses viral replication, but also enhances the virus activation of RIG-I-like receptor-mediated innate immune response.PLoS pathogens · 2022Article
- AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model.PLoS neglected tropical diseases · 2022Article
- INMI1 Zika Virus NS4B Antagonizes the Interferon Signaling by Suppressing STAT1 Phosphorylation.Viruses · 2021Article
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 μM BDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever.
Identifiers
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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.