ArticleProceedings of the National Academy of Sciences of the United States of America2020
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. 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
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
32 citing papers in PubMed, 46 citations in OpenAlex.
- Computational approaches for flavivirus drug discovery: targeting structural and non-structural proteins.RSC medicinal chemistry · 2026Review
- An inactive Zika NS2B-NS3pro protease construct for investigating allosteric inhibitors.Journal of structural biology · 2026Article
- Article
- Integrated Approach of Machine Learning and High-Throughput Screening to Identify Chemical Probe Candidates Targeting Aldehyde Dehydrogenases.ACS pharmacology & translational science · 2025Article
- A quantitative high-throughput screening pipeline to identify small molecule inhibitors of Chikungunya nsP2 protease.Scientific reports · 2025Article
- Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection.Molecular therapy. Nucleic acids · 2025Article
- Discovery of SARS-CoV-2 Nsp14-Methyltransferase (MTase) Inhibitors by Harnessing Scaffold-Centric Exploration of the Ultra Large Chemical Space.ACS pharmacology & translational science · 2025Article
- Applications of Machine Learning Approaches for the Discovery of SARS-CoV-2 PLpro Inhibitors.Journal of chemical information and modeling · 2025Article
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- One size does not fit all: revising traditional paradigms for assessing accuracy of QSAR models used for virtual screening.Journal of cheminformatics · 2025Article
- A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.Viruses · 2025Review
- A high-throughput cell-based screening method for Zika virus protease inhibitor discovery.SLAS discovery : advancing life sciences R & D · 2024Article
- New Insights on Biological Activities, Chemical Compositions, and Classifications of Marine Actinomycetes Antifouling Agents.Microorganisms · 2023Review
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Neurotoxic properties of the Zika virus envelope protein.Experimental neurology · 2023Article
- Article
- Flavivirus proteases: The viral Achilles heel to prevent future pandemics.Antiviral research · 2023Review
- Boroleucine-Derived Covalent Inhibitors of the ZIKV Protease.ChemMedChem · 2023Article
- Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses.PLoS neglected tropical diseases · 2022Review
- Antiviral Agents against Flavivirus Protease: Prospect and Future Direction.Pathogens (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.
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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.