ArticleSignal transduction and targeted therapy2023
SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Host mitochondrial apoptotic signatures in children with chronic conditions reveal viral modulation of MCL-1 in severe SARS-CoV-2 infection.Molecular biology reports · 2026Article
- MCL1 promotes porcine epidemic diarrhea virus replication by modulating arachidonic acid metabolic pathway.PLoS pathogens · 2026Article
- Development of the coronavirus reverse genetic system: Core technology for pathogenesis mechanisms research and vaccine/drug development.Virulence · 2025Review
- Integrative Transcriptomic and Network Pharmacology Analysis Reveals Key Targets and Mechanisms ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity.Cancer gene therapy · 2025Article
- Understanding the mechanisms of mitochondrial rewiring during viral infections.The Journal of general virology · 2025Review
- The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D.Virologica Sinica · 2025Article
- Bid Protein: A Participant in the Apoptotic Network with Roles in Viral Infections.International journal of molecular sciences · 2025Review
- Nucleocapsid Protein of SARS-CoV-2 Upregulates RANTES Expression in A172 Glioblastoma Cells.Molecules (Basel, Switzerland) · 2025Article
- Cell death in acute lung injury: caspase-regulated apoptosis, pyroptosis, necroptosis, and PANoptosis.Frontiers in pharmacology · 2025Review
- Coronavirus nucleocapsid proteins: a multifaceted modulator in the innate immune evasion.Frontiers in microbiology · 2025Review
- The Nucleocapsid (N) Proteins of Different Human Coronaviruses Demonstrate a Variable Capacity to Induce the Formation of Cytoplasmic Condensates.International journal of molecular sciences · 2024Article
- Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.Cell communication and signaling : CCS · 2024Review
- Norovirus-mediated translation repression promotes macrophage cell death.PLoS pathogens · 2024Article
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses.Vaccines · 2024Review
- Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.Nature communications · 2024Article
- Mcl-1 Protein and Viral Infections: A Narrative Review.International journal of molecular sciences · 2024Review
- Persistent microbial infections and idiopathic pulmonary fibrosis - an insight intoFrontiers in cellular and infection microbiology · 2024Review
- Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare.Frontiers in genetics · 2024Article
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn't. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.
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Registered trials
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