ArticleProceedings of the National Academy of Sciences of the United States of America2024
Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed.
- Computational identification of potential inhibitors for chikungunya virus nsP2pro.Royal Society open science · 2026Article
- A nanoluciferase-expressing attenuated CHIKV vaccine strain enables rapid and visual drug screeningJournal of virology · 2026Article
- Functional roles for viral RNA ribosylation in mammalian cells.Nucleic acids research · 2026Article
- Development of Covalent Inhibitors of Chikungunya Virus nsP2 Cysteine Protease Enabled by Direct-to-Biology Synthesis and Screening.Journal of medicinal chemistry · 2026Article
- Recent progress in anti-Chikungunya virus drug discovery: Focus on the viral life cycle and direct-acting antivirals.Virologica Sinica · 2026Review
- Emetine dihydrochloride inhibits Chikungunya virus nsP2 helicase and shows robust antiviral activity in cells and mice.Journal of biomedical science · 2026Article
- Review
- 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
- Chikungunya in 2025: Comprehensive Insights into Virology, Diagnostics, Vaccines, and Antiviral Therapies.Viruses · 2026Review
- Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1.PloS one · 2026Article
- Novel computational pipeline to identify target sites for broad spectrum antiviral drugs.Antiviral research · 2026Article
- Ataxin-2-like promotes translation of nonpolyadenylated reovirus mRNA.Nature communications · 2025Article
- Article
- Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity.Journal of medicinal chemistry · 2025Article
- Unlocking the dual power of Charybdis natator shell: antiviral and larvicidal activities.Bioresources and bioprocessing · 2025Article
- A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity.Protein science : a publication of the Protein Society · 2025Article
- A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity.Scientific reports · 2025Article
- Development of a virulent O'nyong'nyong challenge model to determine heterologous protection mediated by a hydrogen peroxide-inactivated chikungunya virus vaccine.PLoS neglected tropical diseases · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
Corrections and comments
- Update of
Authors and funding
29 authors.
Eric M MertenEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-5306-0790
John D SearsDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-4713-2241
Tina M LeisnerEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-8682-9260
P Brian HardyEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Anirban GhoshalStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0001-9359-6074
Mohammad Anwar HossainStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0001-8684-8755
Kesatebrhan Haile AsressuStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-4803-4739
Peter J BrownStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-8454-0367
Edwin G TseStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-9133-9274
Michael A StashkoEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Kelin LiEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-8630-2928
Jacqueline L Norris-DrouinEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-1193-4514
Laura E HerringProteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-4496-7312
Angie L MordantProteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0002-0151-4498
Thomas S WebbProteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Christine A MillsProteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Natalie K BarkerProteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Zachary J StreblowVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006.
Sumera PerveenStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.ORCID 0000-0002-8898-9540
Cheryl H ArrowsmithStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Rafael Miguez CouñagoStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Jamie J ArnoldDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Craig E CameronDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Daniel N StreblowVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006.
Nathaniel J MoormanDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Mark T HeiseDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0001-5829-8477
Timothy M WillsonStructural Genomics Consortium, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0003-4181-8223
Konstantin I PopovEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Kenneth H PearceEshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.ORCID 0000-0001-8138-5421
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5MResearch Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, WILLSON, TIMOTHY M · 2022 to 2022
$65.5MRequest for a 500 MHz NMR console and nitrogen-cooled cryoprobeS10OD032476 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LEE, ANDREW L · 2022 to 2022
$599kHHS | NIH | National Cancer Institute (NCI) 2P30CA016086-45HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) NIH 1U19AI171292-01NCI NIH HHS P30 CA016086NIAID NIH HHS U19 AI171292NIH HHS S10 OD032476
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics for any alphavirus infection. CHIKV nonstructural protein 2 (nsP2), which contains a cysteine protease domain, is essential for viral replication, making it an attractive target for a drug discovery campaign. Here, we optimized a CHIKV nsP2 protease (nsP2pro) biochemical assay for the screening of a 6,120-compound cysteine-directed covalent fragment library. Using a 50% inhibition threshold, we identified 153 hits (2.5% hit rate). In dose-response follow-up, RA-0002034, a covalent fragment that contains a vinyl sulfone warhead, inhibited CHIKV nsP2pro with an IC
Indexed as
Chikungunya virusCysteine EndopeptidasesAnimalsAntiviral AgentsChikungunya FeverHumansProtease InhibitorsSulfonesVirus ReplicationAntiviral AgentsCysteine EndopeptidasesnsP2 proteinaseProtease InhibitorsSulfoneschikungunya viruscovalent inhibitordrug discoveryfragmentnsP2 protease
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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.