ArticleFrontiers in immunology2022
Z-RNA and the Flipside of the SARS Nsp13 Helicase: Is There a Role for Flipons in Coronavirus-Induced Pathology?
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer.Communications biology · 2026Review
- Structure, Function and Inhibition of Helicases Involved in Virus Infection.Biomolecules · 2026Review
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- The NSP5, ORF6 and NSP13 of SARS-CoV-2 Cooperate to Modulate Inflammatory Cell Death Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins.Open biology · 2025Article
- Monitoring SARS-CoV-2 Nsp13 helicase binding activity using expanded genetic code techniques.RSC chemical biology · 2025Article
- Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling.iScience · 2024Article
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium.Science immunology · 2024Article
- ZBP1 inflames the SARS-CoV-2-infected lung.Cell research · 2023Article
- ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.Molecules (Basel, Switzerland) · 2022Review
- ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We present evidence suggesting that the severe acute respiratory syndrome (SARS) coronavirus non-structural protein 13 (Nsp13) modulates the Z-RNA dependent regulated cell death pathways . We show that Z-prone sequences [called flipons] exist in coronavirus and provide a signature (Z-sig) that enables identification of the animal viruses from which the human pathogens arose. We also identify a potential RIP Homology Interaction Motif (RHIM) in the helicase Nsp13 that resembles those present in proteins that initiate Z-RNA-dependent cell death through interactions with the Z-RNA sensor protein ZBP1. These two observations allow us to suggest a model in which Nsp13 down regulates Z-RNA activated innate immunity by two distinct mechanisms. The first involves a novel ATP-independent Z-flipon helicase (flipase) activity in Nsp13 that differs from that of canonical A-RNA helicases. This flipase prevents formation of Z-RNAs that would otherwise activate cell death pathways. The second mechanism likely inhibits the interactions between ZBP1 and the Receptor Interacting Proteins Kinases RIPK1 and RIPK3 by targeting their RHIM domains. Together the described Nsp13 RHIM and flipase activities have the potential to alter the host response to coronaviruses and impact the design of drugs targeting the Nsp13 protein. The Z-sig and RHIM domains may provide a way of identifying previously uncharacterized viruses that are potentially pathogenic for humans.
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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 Socratic graph.