ArticleCommunications biology2023
ATP and nucleic acids competitively modulate LLPS of the SARS-CoV2 nucleocapsid protein.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Adenosine triphosphate as a modulator of protein interactions and stability.FEBS open bio · 2026Review
- IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.Communications biology · 2026Article
- Review
- Natural product sennoside B disrupts liquid-liquid phase separation of SARS-CoV-2 nucleocapsid protein by inhibiting its RNA-binding activity.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Mechanism-informed identification of FDA-approved topoisomerase inhibitors disrupting SARS-CoV-2 nucleocapsid-RNA interactions.BMC chemistry · 2025Article
- Biomolecular Condensates as Emerging Biomaterials: Functional Mechanisms and Advances in Computational and Experimental Approaches.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- New Advances in Small Molecules Targeted at Viral Capsid-Genome Binding.International journal of molecular sciences · 2025Review
- Dynamic ensembles of SARS-CoV-2 N-protein reveal head-to-head coiled-coil-driven oligomerization and phase separation.Nucleic acids research · 2025Article
- Molecular simulations of enzymatic phosphorylation of disordered proteins and their condensates.Nature communications · 2025Article
- Design and Characterization of DNA-Driven Condensates: Regulating Topology, Mechanical Properties, and Immunorecognition.ACS applied materials & interfaces · 2025Article
- SARS-CoV-2 Is an Electricity-Driven Virus.Reviews of physiology, biochemistry and pharmacology · 2025Review
- The role of the MYL12A liquid-liquid phase separation in neutrophil improves the prognosis of acute respiratory distress syndrome: a multi-omics analysis.Frontiers in immunology · 2025Article
- 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
- In the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.International journal of molecular sciences · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- Synthesis and properties of RNA constrained by a 2'-O-disulfide bridge.ChemistryOpen · 2024Article
- Molecular Mechanisms and Potential Antiviral Strategies of Liquid-Liquid Phase Separation during Coronavirus Infection.Biomolecules · 2024Review
- Adenosine Triphosphate: The Primordial Molecule That Controls Protein Homeostasis and Shapes the Genome-Proteome Interface.Biomolecules · 2024Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 nucleocapsid (N) protein with very low mutation rates is the only structural protein which not only functions to package viral genomic RNA, but also manipulates host-cell machineries, thus representing a key target for drug development. Recent discovery of its liquid-liquid phase separation (LLPS) opens up a new direction for developing anti-SARS-CoV-2 strategies/drugs. However, so far the high-resolution mechanism of its LLPS still remains unknown. Here by DIC and NMR characterization, we have demonstrated: 1) nucleic acids modulate LLPS by dynamic and multivalent interactions over both folded NTD/CTD and Arg/Lys residues within IDRs; 2) ATP with concentrations > mM in all living cells but absent in viruses not only binds NTD/CTD, but also Arg residues within IDRs with a Kd of 2.8 mM; and 3) ATP dissolves nucleic-acid-induced LLPS by competitively displacing nucleic acid from binding the protein. Our study deciphers that the essential binding of N protein with nucleic acid and its LLPS are targetable by small molecules including ATP, which is emerging as a cellular factor controlling the host-SARS-CoV-2 interaction. Fundamentally, our results imply that the mechanisms of LLPS of IDR-containing proteins mediated by ATP and nucleic acids appear to be highly conserved from human to virus.
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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.