ArticleNature chemical biology2016
Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Systematic review and meta-analysis of genome-wide pooled CRISPR screens to identify host factors involved in influenza A virus infection.Journal of virology · 2024Pooled it
- DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells.Nature chemical biology · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Orobas: A computational approach for scoring and analysis of quantitative chemical-genetic interactions from CRISPR-Cas9 screens.STAR protocols · 2026Article
- High-content CRISPR activation screens identify synthetically lethal RNA-based mechanisms to sensitize cancer cells to targeted T cell cytotoxicity.Nature genetics · 2026Article
- Review
- A genome-wide, CRISPR-based screen reveals new requirements for translation initiation and ubiquitination in driving adipogenic fate change.Genes & development · 2025Article
- Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.Science advances · 2025Article
- A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer.Oncogene · 2025Article
- Genes driving three-dimensional growth of immortalized cells and cancer.Cell death & disease · 2025Article
- Translational Pharmacokinetic-Pharmacodynamic Modeling of a Novel Oral Dihydroorotate Dehydrogenase (DHODH) Inhibitor, HOSU-53 (JBZ-001).Pharmaceutics · 2025Article
- Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2025Article
- Drug-target Affinity Prediction by Molecule Secondary Structure Representation Network.Current medicinal chemistry · 2025Article
- CRISPR-based genetic screens advance cancer immunology.Science China. Life sciences · 2024Review
- Review
- GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.Briefings in bioinformatics · 2024Article
- From enhancers to genome conformation: complex transcriptional control underlies expression of a single herpesviral gene.bioRxiv : the preprint server for biology · 2024Article
- Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.JCI insight · 2024Article
- Complex synthetic lethality in cancer.Nature genetics · 2023Review
- The evolving landscape of involvement of DTYMK enzymes in cancer.Medical oncology (Northwood, London, England) · 2023Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Broad-spectrum antiviral drugs targeting host processes could potentially treat a wide range of viruses while reducing the likelihood of emergent resistance. Despite great promise as therapeutics, such drugs remain largely elusive. Here we used parallel genome-wide high-coverage short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screens to identify the cellular target and mechanism of action of GSK983, a potent broad-spectrum antiviral with unexplained cytotoxicity. We found that GSK983 blocked cell proliferation and dengue virus replication by inhibiting the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH). Guided by mechanistic insights from both genomic screens, we found that exogenous deoxycytidine markedly reduced GSK983 cytotoxicity but not antiviral activity, providing an attractive new approach to improve the therapeutic window of DHODH inhibitors against RNA viruses. Our results highlight the distinct advantages and limitations of each screening method for identifying drug targets, and demonstrate the utility of parallel knockdown and knockout screens for comprehensive probing of drug activity.
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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.