ArticlePLoS pathogens2022
SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- NADThe Journal of general virology · 2026Review
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- SIRT5: a potential target for discovering bioactive natural products.Journal of natural medicines · 2025Review
- SIRT5-mediated desuccinylation of the porcine deltacoronavirus M protein drives pexophagy to enhance viral proliferation.PLoS pathogens · 2025Article
- Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response.Viruses · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Article
- Expression of metabolic genes in NK cells is associated with clinical outcomes in patients with severe COVID-19: a brief report.Frontiers in cellular and infection microbiology · 2025Article
- Decoding NAD+ Metabolism in COVID-19: Implications for Immune Modulation and Therapy.Vaccines · 2024Review
- SIRT5 suppresses the trophoblast cell proliferation, invasion, and migration to promote preeclampsia via desuccinylating HOXB3.Journal of assisted reproduction and genetics · 2024Article
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.Cell communication and signaling : CCS · 2024Review
- The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- SIRT3 Activation a Promise in Drug Development? New Insights into SIRT3 Biology and Its Implications on the Drug Discovery Process.Journal of medicinal chemistry · 2024Review
- Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein.Virology journal · 2023Article
- Orchestration of Mitochondrial Function and Remodeling by Post-Translational Modifications Provide Insight into Mechanisms of Viral Infection.Biomolecules · 2023Review
- From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.International journal of molecular sciences · 2023Review
- Review
- Sirt1 Negatively Regulates Cellular Antiviral Responses by Preventing the Cytoplasmic Translocation of Interferon-Inducible Protein 16 in Human Cells.Journal of virology · 2023Article
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16 authors at 4 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response, independently of the Mitochondrial Antiviral Signaling Protein MAVS. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.
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