ArticleThe Journal of clinical investigation2023
An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 24 citations in OpenAlex.
- Substrate-Selective Inhibition of the SARS-CoV-2 Papain-Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NADThe Journal of general virology · 2026Review
- Divergent inflammatory and neurology-related protein levels in long COVID following primary and breakthrough SARS-CoV-2 infections.Communications medicine · 2026Article
- Structure-Guided Optimization and Biological Validation of 1,3,4-Thiadiazole-Based SIRT2 Inhibitors Reinforcing Channel Entrance Interactions.Drug development research · 2026Article
- From Pharmacophore to Warhead: NADAngewandte Chemie (International ed. in English) · 2025Article
- Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling.Antiviral research · 2025Article
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions.Journal of medicinal chemistry · 2025Article
- Proceedings of the second annual dengue endgame summit: A call to action.PLoS neglected tropical diseases · 2025Article
- Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Sirtuin 2 inhibitor AGK2 exerts antiviral effects by inducing epigenetic suppression of hepatitis B virus covalently closed circular DNA through recruitment of repressive histone lysine methyltransferases and reduction of cccDNA.Frontiers in cellular and infection microbiology · 2025Article
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Predictors of mortality among critically ill SARS-CoV-2 infected patients-a retrospective cohort study, Kerala, India.Frontiers in public health · 2025Article
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- An allosteric inhibitor of sirtuin 2 blocks hepatitis B virus covalently closed circular DNA establishment and its transcriptional activity.Antiviral research · 2024Article
- A homogeneous time-resolved fluorescence screen to identify SIRT2 deacetylase and defatty-acylase inhibitors.PloS one · 2024Article
- 5-((3-Amidobenzyl)oxy)nicotinamides as SIRT2 Inhibitors: A Study of Constrained Analogs.Molecules (Basel, Switzerland) · 2023Article
- Inhibition of SIRT2 promotes death of human cytomegalovirus-infected peripheral blood monocytes via apoptosis and necroptosis.Antiviral research · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Most drugs used to treat viral disease target a virus-coded product. They inhibit a single virus or virus family, and the pathogen can readily evolve resistance. Host-targeted antivirals can overcome these limitations. The broad-spectrum activity achieved by host targeting can be especially useful in combating emerging viruses and for treatment of diseases caused by multiple viral pathogens, such as opportunistic agents in immunosuppressed patients. We have developed a family of compounds that modulate sirtuin 2, an NAD+-dependent deacylase, and now report the properties of a member of that family, FLS-359. Biochemical and x-ray structural studies show that the drug binds to sirtuin 2 and allosterically inhibits its deacetylase activity. FLS-359 inhibits the growth of RNA and DNA viruses, including members of the coronavirus, orthomyxovirus, flavivirus, hepadnavirus, and herpesvirus families. FLS-359 acts at multiple levels to antagonize cytomegalovirus replication in fibroblasts, causing modest reductions in viral RNAs and DNA, together with a much greater reduction in infectious progeny, and it exhibits antiviral activity in humanized mouse models of infection. Our results highlight the potential of sirtuin 2 inhibitors as broad-spectrum antivirals and set the stage for further understanding of how host epigenetic mechanisms impact the growth and spread of viral pathogens.
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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.