ArticleProceedings of the National Academy of Sciences of the United States of America2022
SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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
27 citing papers in PubMed, 40 citations in OpenAlex.
- Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.Clinical proteomics · 2026Review
- African swine fever virus hijacks host pyrimidine metabolism to promote viral replication.Journal of virology · 2025Article
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.Molecular biology and evolution · 2025Article
- Article
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- Metabolic Reprogramming in Respiratory Viral Infections: A Focus on SARS-CoV-2, Influenza, and Respiratory Syncytial Virus.Biomolecules · 2025Review
- Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection.PLoS pathogens · 2025Article
- Article
- Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.Virologica Sinica · 2025Article
- Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection.PLoS pathogens · 2025Article
- Astragaloside IV mitigates influenza-induced inflammatory responses by suppressing the Wnt/β-catenin signalling pathway in alveolar macrophages.Veterinary research · 2025Article
- SARS-CoV-2 nucleocapsid protein induces a Mincle-dependent macrophage inflammatory response in acute kidney injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Analysis of Metabolomic Reprogramming Induced by Infection with Kaposi's Sarcoma-Associated Herpesvirus Using Untargeted Metabolomic Profiling.International journal of molecular sciences · 2025Article
- The Loop-In Binding Mode of Dihydroorotase: Implications for Ligand Binding and Therapeutic Targeting.International journal of molecular sciences · 2025Review
- Pyrimidine synthesis enzyme CTP synthetase 1 suppresses antiviral interferon induction by deamidating IRF3.Immunity · 2025Article
- Metabolic Pathways Affected in Patients Undergoing Hemodialysis and Their Relationship with Inflammation.International journal of molecular sciences · 2024Article
- Article
- Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus.Nature communications · 2024Article
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
- Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.
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What OpenQuestion holds
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.