ArticlePloS one2021
Pyrimidone inhibitors targeting Chikungunya Virus nsP3 macrodomain by fragment-based drug design.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Syndirella: synthesis-directed fragment elaboration enables extensive and cost-effective binding site exploration beyond catalog compounds.Chemical science · 2026Article
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- Recent advances in antiviral drugs for Chikungunya virus (CHIKV): Targets, mechanisms, and development strategies.Acta pharmaceutica Sinica. B · 2026Review
- Discovery of BPR2-D2 compound in inhibiting Chikungunya viral RNA synthesis by replicon systems.Biomedical journal · 2026Article
- Bioisosteric and Virtual Screening Approach to Identify Natural Inhibitors of Chikunguya alphavirus nsP3.Cell biochemistry and biophysics · 2025Article
- Phenol and chromone compounds forPharmaceutical science advances · 2025Article
- Chlorinated biscoumarins inhibit chikungunya virus replication in cell-based and animal models.Emerging microbes & infections · 2025Article
- A Review of the Biology of Chikungunya Virus Highlighting the Development of Current Novel Therapeutic and Prevention Approaches.Pathogens (Basel, Switzerland) · 2025Review
- Article
- Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection ofbioRxiv : the preprint server for biology · 2025Article
- Structural Features of Nucleoproteins from the Recently DiscoveredInternational journal of molecular sciences · 2025Article
- Derivatives of MOPS: promising scaffolds for SARS coronaviruses Macro domain-targeted inhibition.The FEBS journal · 2025Article
- Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection.PLoS pathogens · 2024Article
- Identifying novel chemical matter against the Chikungunya virus nsP3 macrodomain through crystallographic fragment screening.bioRxiv : the preprint server for biology · 2024Article
- New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease MACS omega · 2024Article
- Article
- Advances in the Development of Non-Structural Protein 1 (NsP1) Inhibitors for the Treatment of Chikungunya Virus Infection.Mini reviews in medicinal chemistry · 2024Review
- The 8-bromobaicalein alleviated chikungunya-induced musculoskeletal inflammation and reduced the viral load in healthy adult mice.Emerging microbes & infections · 2023Article
- Host Factor Nucleophosmin 1 (NPM1/B23) Exerts Antiviral Effects against Chikungunya Virus by Its Interaction with Viral Nonstructural Protein 3.Microbiology spectrum · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The macrodomain of nsP3 (nsP3MD) is highly conserved among the alphaviruses and ADP-ribosylhydrolase activity of Chikungunya Virus (CHIKV) nsP3MD is critical for CHIKV viral replication and virulence. No small molecule drugs targeting CHIKV nsP3 have been identified to date. Here we report small fragments that bind to nsP3MD which were discovered by virtually screening a fragment library and X-ray crystallography. These identified fragments share a similar scaffold, 2-pyrimidone-4-carboxylic acid, and are specifically bound to the ADP-ribose binding site of nsP3MD. Among the fragments, 2-oxo-5,6-benzopyrimidine-4-carboxylic acid showed anti-CHIKV activity with an IC50 of 23 μM. Our fragment-based drug discovery approach provides valuable information to further develop a specific and potent nsP3 inhibitor of CHIKV viral replication based on the 2-pyrimidone-4-carboxylic acid scaffold. In silico studies suggest this pyrimidone scaffold could also bind to the macrodomains of other alphaviruses and coronaviruses and thus, have potential pan-antiviral 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.