ArticleNucleic acids research2012
Bulged DNA substrates for identifying poxvirus resolvase inhibitors.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- The next generation of orthopoxvirus antivirals: preparing for future threats.Future medicinal chemistry · 2026Article
- Discovery and characterization of a hydroxypyridone-3-carboxamide analog as an antiviral lead against orthopoxviruses.Antimicrobial agents and chemotherapy · 2026Article
- Design and Multi-Level Biological Evaluation of Naphthyridine-Based Derivatives as Topoisomerase I/II-Targeted Anticancer Agents with Anti-Fowlpox Virus Activity Supported by In Silico Analysis.International journal of molecular sciences · 2026Article
- 1-Hydroxy-1,8-napthyridinone (DHN) Analogs Potently Inhibit Monkeypox Virus Resolvase (Mpr).Journal of medicinal chemistry · 2026Article
- Discovery and Characterization of a Hydroxypyridone-3-carboxamide Analog as an Antiviral Lead against Orthopoxviruses.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Small-Molecule Orthopoxvirus Resolvase Inhibitors with Antiviral Activity.Journal of medicinal chemistry · 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
- Viral Nucleases.Viruses · 2023Article
- Structural insights into the promiscuous DNA binding and broad substrate selectivity of fowlpox virus resolvase.Scientific reports · 2020Article
- Structure and Metal Binding Properties of a Poxvirus Resolvase.The Journal of biological chemistry · 2016Article
- Targets for Combating the Evolution of Acquired Antibiotic Resistance.Biochemistry · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Resolvase enzymes that cleave DNA four-way (Holliday) junctions are required for poxvirus replication, but clinically useful inhibitors have not been developed. Here, we report an assay for resolvase cleavage activity based on fluorescence polarization (FP) for high-throughput screening and mechanistic studies. Initial analysis showed that cleavage of a fluorescently labeled Holliday junction substrate did not yield an appreciable change in FP, probably because the cleavage product did not have sufficiently increased mobility to yield a strong FP signal. Iterative optimization yielded a substrate with an off-center DNA bulge, which after cleavage released a labeled short stand and yielded a greatly reduced FP signal. Using this assay, 133,000 compounds were screened, identifying 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds as inhibitors. Structure-activity studies revealed functional parallels to Food and Drug Administration (FDA)-approved drugs targeting the related human immunodeficiency virus integrase enzyme. Some 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds showed anti-poxvirus activity.
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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.