Skip to content
2000
Volume 26, Issue 10
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

Abstract

COVID-19 is a respiratory disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but because the receptor protein of this virus can appear not only in the lungs and throat but also in various parts of the host's body, it causes different diseases. Recent observations have suggested that SARS-CoV-2 damages the central nervous system of patients in a manner similar to amyloid-associated neurodegenerative diseases such as Alzheimer's and Parkinson's. Neurodegenerative diseases are believed to be associated with the self-assembly of amyloid proteins and peptides. On the other hand, whole proteins or parts of them encoded by SARS-CoV-2 can form amyloid fibrils, which may play an important role in amyloid-related diseases. Motivated by this evidence, this mini-review discusses experimental and computational studies of SARS-CoV-2 proteins that can form amyloid aggregates. Liquid-Liquid Phase Separation (LLPS) is a dynamic and reversible process leading to the creation of membrane-less organelles within the cytoplasm, which is not bound by a membrane that concentrates specific types of biomolecules. These organelles play pivotal roles in cellular signaling, stress response, and the regulation of biomolecular condensates. Recently, LLPS of the Nucleocapsid (N) protein and SARS-CoV-2 RNA has been disclosed, but many questions about the phase separation mechanism and the formation of the virion core are still unclear. We summarize the results of this phenomenon and suggest potentially intriguing issues for future research.

Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037354482250414045355
2025-05-08
2025-12-19
Loading full text...

Full text loading...

References

  1. SalamannaF. MaglioM. LandiniM.P. FiniM. Body localization of ace-2: On the trail of the keyhole of SARS-COV-2.Front. Med.2020759449510.3389/fmed.2020.59449533344479
    [Google Scholar]
  2. SongE. ZhangC. IsraelowB. Lu-CulliganA. PradoA.V. SkriabineS. LuP. WeizmanO.E. LiuF. DaiY. Szigeti-BuckK. YasumotoY. WangG. CastaldiC. HeltkeJ. NgE. WheelerJ. AlfajaroM.M. LevavasseurE. FontesB. RavindraN.G. DijkV.D. ManeS. GunelM. RingA. KazmiS.A.J. ZhangK. WilenC.B. HorvathT.L. PluI. HaikS. ThomasJ.L. LouviA. FarhadianS.F. HuttnerA. SeilheanD. RenierN. BilguvarK. IwasakiA. Neuroinvasion of SARS-COV-2 in human and mouse brain.J. Exp. Med.20212183e2020213510.1084/jem.2020213533433624
    [Google Scholar]
  3. MatschkeJ. LütgehetmannM. HagelC. SperhakeJ.P. SchröderA.S. EdlerC. MushumbaH. FitzekA. AllweissL. DandriM. DottermuschM. HeinemannA. PfefferleS. SchwabenlandM. MagruderS.D. BonnS. PrinzM. GerloffC. PüschelK. KrasemannS. AepfelbacherM. GlatzelM. Neuropathology of patients with COVID-19 in Germany: A post- mortem case series.Lancet Neurol.2020191191992910.1016/S1474‑4422(20)30308‑233031735
    [Google Scholar]
  4. FronteraJ.A. YangD. LewisA. PatelP. MedicherlaC. ArenaV. FangT. AndinoA. SnyderT. MadhavanM. GratchD. FuchsB. DessyA. CanizaresM. JaureguiR. ThomasB. BaumanK. OliveraA. BhagatD. SonsonM. ParkG. StainmanR. SunwooB. TalmasovD. TamimiM. ZhuY. RosenthalJ. DygertL. RisticM. IshiiH. ValdesE. OmariM. GurinL. HuangJ. CzeislerB.M. KahnD.E. ZhouT. LinJ. LordA.S. MelmedK. MeropolS. TroxelA.B. PetkovaE. WisniewskiT. BalcerL. MorrisonC. YaghiS. GalettaS. A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.J. Neurol. Sci.202142611748610.1016/j.jns.2021.11748634000678
    [Google Scholar]
  5. EllulM.A. BenjaminL. SinghB. LantS. MichaelB.D. EastonA. KneenR. DefresS. SejvarJ. SolomonT. Neurological associations of COVID-19.Lancet Neurol.202019976778310.1016/S1474‑4422(20)30221‑032622375
    [Google Scholar]
  6. BonhenryD. CharnleyM. GonçalvesJ. HammarströmP. HenekaM.T. ItzhakiR. LambertJ.C. MannanM. BaigA.M. MiddeldorpJ. NyströmS. ReynoldsN.P. StefanatouM. BerrymanJ.T. SARS-COV-2 infection as a cause of neurodegeneration.Lancet Neurol.202423656256310.1016/S1474‑4422(24)00178‑938760096
    [Google Scholar]
  7. DjordjevicJ. Jones-GotmanM. SousaD.K. ChertkowH. Olfaction in patients with mild cognitive impairment and Alzheimer’s disease.Neurobiol. Aging200829569370610.1016/j.neurobiolaging.2006.11.01417207898
    [Google Scholar]
  8. BhardwajT. GadhaveK. KapugantiS.K. KumarP. BrotzakisZ.F. SaumyaK.U. NayakN. KumarA. JoshiR. MukherjeeB. BhardwajA. ThakurK.G. GargN. VendruscoloM. GiriR. Amyloidogenic proteins in the SARS-CoV and SARS-COV-2 proteomes.Nat. Commun.202314194510.1038/s41467‑023‑36234‑436806058
    [Google Scholar]
  9. NguyenP.H. RamamoorthyA. SahooB.R. ZhengJ. FallerP. StraubJ.E. DominguezL. SheaJ.E. DokholyanN.V. SimoneD.A. MaB. NussinovR. NajafiS. NgoS.T. LoquetA. ChiricottoM. GangulyP. McCartyJ. LiM.S. HallC. WangY. MillerY. MelchionnaS. HabensteinB. TimrS. ChenJ. HnathB. StrodelB. KayedR. LesnéS. WeiG. SterponeF. DoigA.J. DerreumauxP. Amyloid oligomers: A joint experimental/computational perspective on Alzheimer’s disease, Parkinson’s disease, type II diabetes, and amyotrophic lateral sclerosis.Chem. Rev.202112142545264710.1021/acs.chemrev.0c0112233543942
    [Google Scholar]
  10. ChitiF. DobsonC.M. Protein misfolding, functional amyloid, and human disease.Annu. Rev. Biochem.200675133336610.1146/annurev.biochem.75.101304.12390116756495
    [Google Scholar]
  11. KarranE. StrooperD.B. The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics.Nat. Rev. Drug Discov.202221430631810.1038/s41573‑022‑00391‑w35177833
    [Google Scholar]
  12. CalabresiP. MechelliA. NataleG. Volpicelli-DaleyL. LazzaroD.G. GhiglieriV. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction.Cell Death Dis.202314317610.1038/s41419‑023‑05672‑936859484
    [Google Scholar]
  13. Rudnicka-DrożakE. DrożakP. MizerskiG. ZaborowskiT. ŚlusarskaB. NowickiG. DrożakM. Links between COVID-19 and Alzheimer’s disease—what do we already know?Int. J. Environ. Res. Public Health2023203214610.3390/ijerph2003214636767513
    [Google Scholar]
  14. ShajahanS.R. KumarS. RamliM.D.C. Unravelling the connection between COVID-19 and Alzheimer’s disease: A comprehensive review.Front. Aging Neurosci.202415127445210.3389/fnagi.2023.127445238259635
    [Google Scholar]
  15. AlbertiS. GladfelterA. MittagT. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates.Cell2019176341943410.1016/j.cell.2018.12.03530682370
    [Google Scholar]
  16. BroccaS. GrandoriR. LonghiS. UverskyV. Liquid–liquid phase separation by intrinsically disordered protein regions of viruses: Roles in viral life cycle and control of virus–host interactions.Int. J. Mol. Sci.20202123904510.3390/ijms2123904533260713
    [Google Scholar]
  17. DignonG.L. BestR.B. MittalJ. Biomolecular phase separation: From molecular driving forces to macroscopic properties.Annu. Rev. Phys. Chem.2020711537510.1146/annurev‑physchem‑071819‑11355332312191
    [Google Scholar]
  18. DasS. LinY.H. VernonR.M. Forman-KayJ.D. ChanH.S. Comparative roles of charge, π, and hydrophobic interactions in sequence-dependent phase separation of intrinsically disordered proteins.Proc. Natl. Acad. Sci. USA202011746287952880510.1073/pnas.200812211733139563
    [Google Scholar]
  19. WangB. ZhangL. DaiT. QinZ. LuH. ZhangL. ZhouF. Liquid–liquid phase separation in human health and diseases.Signal Transduct. Target. Ther.20216129010.1038/s41392‑021‑00678‑134334791
    [Google Scholar]
  20. BananiS.F. LeeH.O. HymanA.A. RosenM.K. Biomolecular condensates: Organizers of cellular biochemistry.Nat. Rev. Mol. Cell Biol.201718528529810.1038/nrm.2017.728225081
    [Google Scholar]
  21. ChenH. CuiY. HanX. HuW. SunM. ZhangY. WangP.H. SongG. ChenW. LouJ. Liquid–liquid phase separation by SARS-COV-2 nucleocapsid protein and RNA.Cell Res.202030121143114510.1038/s41422‑020‑00408‑232901111
    [Google Scholar]
  22. PerdikariT.M. MurthyA.C. RyanV.H. WattersS. NaikM.T. FawziN.L. SARS-CoV-2 nucleocapsid protein phase-separates with RNA and with human hnRNPs.EMBO J.20203924e10647810.15252/embj.202010647833200826
    [Google Scholar]
  23. CubukJ. AlstonJ.J. InciccoJ.J. SinghS. Stuchell-BreretonM.D. WardM.D. ZimmermanM.I. VithaniN. GriffithD. WagonerJ.A. BowmanG.R. HallK.B. SorannoA. HolehouseA.S. The SARS-COV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA.Nat. Commun.2021121193610.1038/s41467‑021‑21953‑333782395
    [Google Scholar]
  24. BoeynaemsS. AlbertiS. FawziN.L. MittagT. PolymenidouM. RousseauF. SchymkowitzJ. ShorterJ. WolozinB. BoschD.V.L. TompaP. FuxreiterM. Protein phase separation: A new phase in cell biology.Trends Cell Biol.201828642043510.1016/j.tcb.2018.02.00429602697
    [Google Scholar]
  25. ShinY. BrangwynneC.P. Liquid phase condensation in cell physiology and disease.Science20173576357eaaf438210.1126/science.aaf438228935776
    [Google Scholar]
  26. HymanA.A. WeberC.A. JülicherF. Liquid-liquid phase separation in biology.Annu. Rev. Cell Dev. Biol.2014301395810.1146/annurev‑cellbio‑100913‑01332525288112
    [Google Scholar]
  27. KimD. LeeJ.Y. YangJ.S. KimJ.W. KimV.N. ChangH. The architecture of SARS-COV-2 transcriptome.Cell20201814914921.e1010.1016/j.cell.2020.04.01132330414
    [Google Scholar]
  28. GordonD.E. JangG.M. BouhaddouM. XuJ. ObernierK. WhiteK.M. O’MearaM.J. RezeljV.V. GuoJ.Z. SwaneyD.L. TumminoT.A. HüttenhainR. KaakeR.M. RichardsA.L. TutuncuogluB. FoussardH. BatraJ. HaasK. ModakM. KimM. HaasP. PolaccoB.J. BrabergH. FabiusJ.M. EckhardtM. SoucherayM. BennettM.J. CakirM. McGregorM.J. LiQ. MeyerB. RoeschF. ValletT. KainM.A. MiorinL. MorenoE. NaingZ.Z.C. ZhouY. PengS. ShiY. ZhangZ. ShenW. KirbyI.T. MelnykJ.E. ChorbaJ.S. LouK. DaiS.A. Barrio-HernandezI. MemonD. Hernandez-ArmentaC. LyuJ. MathyC.J.P. PericaT. PillaK.B. GanesanS.J. SaltzbergD.J. RakeshR. LiuX. RosenthalS.B. CalvielloL. VenkataramananS. Liboy-LugoJ. LinY. HuangX.P. LiuY. WankowiczS.A. BohnM. SafariM. UgurF.S. KohC. SavarN.S. TranQ.D. ShengjulerD. FletcherS.J. O’NealM.C. CaiY. ChangJ.C.J. BroadhurstD.J. KlippstenS. SharpP.P. WenzellN.A. Kuzuoglu-OzturkD. WangH.Y. TrenkerR. YoungJ.M. CaveroD.A. HiattJ. RothT.L. RathoreU. SubramanianA. NoackJ. HubertM. StroudR.M. FrankelA.D. RosenbergO.S. VerbaK.A. AgardD.A. OttM. EmermanM. JuraN. ZastrowV.M. VerdinE. AshworthA. SchwartzO. d’EnfertC. MukherjeeS. JacobsonM. MalikH.S. FujimoriD.G. IdekerT. CraikC.S. FloorS.N. FraserJ.S. GrossJ.D. SaliA. RothB.L. RuggeroD. TauntonJ. KortemmeT. BeltraoP. VignuzziM. García-SastreA. ShokatK.M. ShoichetB.K. KroganN.J. A SARS-COV-2 protein interaction map reveals targets for drug repurposing.Nature2020583781645946810.1038/s41586‑020‑2286‑932353859
    [Google Scholar]
  29. YangH. RaoZ. Structural biology of SARS-COV-2 and implications for therapeutic development.Nat. Rev. Microbiol.2021191168570010.1038/s41579‑021‑00630‑834535791
    [Google Scholar]
  30. NyströmS. HammarströmP. Amyloidogenesis of SARS-COV-2 Spike Protein.J. Am. Chem. Soc.2022144208945895010.1021/jacs.2c0392535579205
    [Google Scholar]
  31. CaoS. SongZ. RongJ. AndrikopoulosN. LiangX. WangY. PengG. DingF. KeP.C. Spike protein fragments promote alzheimer’s amyloidogenesis.ACS Appl. Mater. Interfaces20231534403174032910.1021/acsami.3c0981537585091
    [Google Scholar]
  32. MorozovaO.V. ManuveraV.A. BarinovN.A. SubchevaE.N. LaktyushkinV.S. IvanovD.A. LazarevV.N. KlinovD.V. Self-assembling amyloid-like nanostructures from SARS-COV-2 S1, S2, RBD and N recombinant proteins.Arch. Biochem. Biophys.202475210984310.1016/j.abb.2023.10984338072298
    [Google Scholar]
  33. YeQ. WestA.M.V. SillettiS. CorbettK.D. Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.Protein Sci.20202991890190110.1002/pro.390932654247
    [Google Scholar]
  34. Tayeb-FligelmanE. BowlerJ.T. TaiC.E. SawayaM.R. JiangY.X. GarciaG.Jr GrinerS.L. ChengX. SalwinskiL. LutterL. SeidlerP.M. LuJ. RosenbergG.M. HouK. AbskharonR. PanH. ZeeC.T. BoyerD.R. LiY. AndersonD.H. MurrayK.A. FalconG. CascioD. SaelicesL. DamoiseauxR. ArumugaswamiV. GuoF. EisenbergD.S. Low complexity domains of the nucleocapsid protein of SARS-COV-2 form amyloid fibrils.Nat. Commun.2023141237910.1038/s41467‑023‑37865‑337185252
    [Google Scholar]
  35. NadyA. ReichheldS.E. SharpeS. An amyloidogenic fragment of the SARS CoV-2 envelope protein promotes serum amyloid A misfolding and fibrillization.bioRxiv20241910.1101/2024.04.25.591137
    [Google Scholar]
  36. GengH. SubramanianS. WuL. BuH.F. WangX. DuC. PlaenD.I.G. TanX.D. SARS-COV-2 ORF8 forms intracellular aggregates and inhibits ifnγ-induced antiviral gene expression in human lung epithelial cells.Front. Immunol.20211267948210.3389/fimmu.2021.67948234177923
    [Google Scholar]
  37. NishideG. LimK. TamuraM. KobayashiA. ZhaoQ. HazawaM. AndoT. NishidaN. WongR.W. Nanoscopic elucidation of spontaneous self-assembly of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) open reading frame 6 (orf6) protein.J. Phys. Chem. Lett.202314388385839610.1021/acs.jpclett.3c0144037707320
    [Google Scholar]
  38. CharnleyM. IslamS. BindraG.K. EngwirdaJ. RatcliffeJ. ZhouJ. MezzengaR. HulettM.D. HanK. BerrymanJ.T. ReynoldsN.P. Neurotoxic amyloidogenic peptides in the proteome of SARS-COV-2: Potential implications for neurological symptoms in COVID-19.Nat. Commun.2022131338710.1038/s41467‑022‑30932‑135697699
    [Google Scholar]
  39. SanislavO. TetajR. Metali RatcliffeJ. PhillipsW. KleinA.R. SethiA. ZhouJ. MezzengaR. SaxerS.S. CharnleyM. AnnesleyS.J. ReynoldsN.P. Cell invasive amyloid assemblies from SARS-COV-2 peptides can form multiple polymorphs with varying neurotoxicity.Nanoscale20241642198141982710.1039/D4NR03030C39363846
    [Google Scholar]
  40. WölkC. ShenC. HauseG. SuryaW. TorresJ. HarveyR.D. BelloG. Membrane condensation and curvature induced by SARS-COV-2 envelope protein.Langmuir20244052646265510.1021/acs.langmuir.3c0307938258382
    [Google Scholar]
  41. MehreganA. Pérez-ConesaS. ZhuangY. ElbahnsiA. PasiniD. LindahlE. HowardR.J. UlensC. DelemotteL. Probing effects of the SARS-COV-2 E protein on membrane curvature and intracellular calcium.Biochim. Biophys. Acta Biomembr.202218641018399410.1016/j.bbamem.2022.18399435724739
    [Google Scholar]
  42. BilogM. CersosimoJ. VigilI. DesameroR.Z.B. ProfitA.A. Effect of a SARS-COV-2 protein fragment on the amyloidogenic propensity of human islet amyloid polypeptide.ACS Chem. Neurosci.202415244431444010.1021/acschemneuro.4c0047339582236
    [Google Scholar]
  43. LeeJ.G. HuangW. LeeH. LeemputD.V.J. KaneM.A. HanZ. Characterization of SARS-COV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by selinexor.Cell Biosci.20211115810.1186/s13578‑021‑00568‑733766124
    [Google Scholar]
  44. YooT.Y. MitchisonT.J. Quantitative comparison of nuclear transport inhibition by SARS coronavirus ORF6 reveals the importance of oligomerization.Proc. Natl. Acad. Sci. USA20241214e230799712110.1073/pnas.230799712138236733
    [Google Scholar]
  45. BucciantiniM. RigacciS. StefaniM. Amyloid aggregation: Role of biological membranes and the aggregate–membrane system.J. Phys. Chem. Lett.20145351752710.1021/jz402435426276603
    [Google Scholar]
  46. NguyenH.L. LinhH.Q. KrupaP. PennaL.G. LiM.S. Amyloid β dodecamer disrupts the neuronal membrane more strongly than the mature fibril: Understanding the role of oligomers in neurotoxicity.J. Phys. Chem. B2022126203659367210.1021/acs.jpcb.2c0176935580354
    [Google Scholar]
  47. JanaA.K. GreenwoodA.B. HansmannU.H.E. Presence of a SARS-COV-2 protein enhances amyloid formation of serum amyloid A.J. Phys. Chem. B2021125329155916710.1021/acs.jpcb.1c0487134370466
    [Google Scholar]
  48. JanaA.K. LanderC.W. ChesneyA.D. HansmannU.H.E. Effect of an amyloidogenic SARS-COV-2 protein fragment on α-synuclein monomers and fibrils.J. Phys. Chem. B2022126203648365810.1021/acs.jpcb.2c0125435580331
    [Google Scholar]
  49. IslamS. ParvesM.R. IslamM.J. AliM.A. EfazF.M. HossainM.S. UllahM.O. HalimM.A. Structural and functional effects of the L84S mutant in the SARS-COV-2 ORF8 dimer based on microsecond molecular dynamics study.J. Biomol. Struct. Dyn.202442115770578710.1080/07391102.2023.222891937403295
    [Google Scholar]
  50. GadhaveK. KumarP. KumarA. BhardwajT. GargN. GiriR. Conformational dynamics of 13 amino acids long NSP11 of SARS-COV-2 under membrane mimetics and different solvent conditions.Microb. Pathog.202115810504110.1016/j.micpath.2021.10504134119626
    [Google Scholar]
  51. KumarA. KumarP. SaumyaK.U. GiriR. Investigating the conformational dynamics of SARS-COV-2 NSP6 protein with emphasis on non-transmembrane 91–112 & 231–290 regions.Microb. Pathog.2021161Pt A10523610.1016/j.micpath.2021.10523634648928
    [Google Scholar]
  52. FengS. O’BrienA. ChenD.Y. SaeedM. BakerS.C. SARS-COV-2 nonstructural protein 6 from Alpha to Omicron: Evolution of a transmembrane protein.MBio2023144e00688-2310.1128/mbio.00688‑2337477426
    [Google Scholar]
  53. GarmayY. RubelA. EgorovV. Peptide from NSP7 is able to form amyloid-like fibrils: Artifact or challenge to drug design?Biochim. Biophys. Acta. Proteins Proteomics20231871214088410.1016/j.bbapap.2022.14088436462605
    [Google Scholar]
  54. WuZ. ZhangX. HuangZ. MaK. SARS-COV-2 proteins interact with alpha synuclein and induce lewy body-like pathology in vitro.Int. J. Mol. Sci.2022236339410.3390/ijms2306339435328814
    [Google Scholar]
  55. SemerdzhievS.A. FakhreeM.A.A. Segers-NoltenI. BlumC. ClaessensM.M.A.E. Interactions between SARS-COV-2 n-protein and α-synuclein accelerate amyloid formation.ACS Chem. Neurosci.202213114315010.1021/acschemneuro.1c0066634860005
    [Google Scholar]
  56. SemerdzhievS.A. Segers-NoltenI. SchootD.V.P. BlumC. ClaessensM.M.A.E. SARS-COV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils.Nanoscale20231545183371834610.1039/D3NR03556E37921451
    [Google Scholar]
  57. PhilippensI.H.C.H.M. BöszörményiK.P. WubbenJ.A.M. FagrouchZ.C. DrielV.N. MayenburgA.Q. LozovagiaD. RoosE. SchurinkB. BugianiM. BontropR.E. MiddeldorpJ. BogersW.M. Geus-OeiD.L.F. LangermansJ.A.M. VerschoorE.J. StammesM.A. VerstrepenB.E. Brain inflammation and intracellular α-synuclein aggregates in macaques after SARS-COV-2 infection.Viruses202214477610.3390/v1404077635458506
    [Google Scholar]
  58. ChenJ. ChenJ. LeiZ. ZhangF. ZengL.H. WuX. LiS. TanJ. Amyloid precursor protein facilitates SARS-COV-2 virus entry into cells and enhances amyloid-β-associated pathology in APP/PS1 mouse model of Alzheimer’s disease.Transl. Psychiatry202313139610.1038/s41398‑023‑02692‑z38104129
    [Google Scholar]
  59. CamachoR.C. AlabedS. ZhouH. ChangS.L. Network meta- analysis on the changes of amyloid precursor protein expression following SARS-COV-2 infection.J. Neuroimmune Pharmacol.202116475676910.1007/s11481‑021‑10012‑934757528
    [Google Scholar]
  60. LiY. LuS. GuJ. XiaW. ZhangS. ZhangS. WangY. ZhangC. SunY. LeiJ. LiuC. SuZ. YangJ. PengX. LiD. SARS-COV-2 impairs the disassembly of stress granules and promotes als-associated amyloid aggregation.Protein Cell202213860261410.1007/s13238‑022‑00905‑735384603
    [Google Scholar]
  61. RamaniA. MüllerL. OstermannP.N. GabrielE. Abida-IslamP. Müller-SchiffmannA. MariappanA. GoureauO. GruellH. WalkerA. AndréeM. HaukaS. HouwaartT. DiltheyA. WohlgemuthK. OmranH. KleinF. WieczorekD. AdamsO. TimmJ. KorthC. SchaalH. GopalakrishnanJ. SARS-CoV-2 targets neurons of 3D human brain organoids.EMBO J.20203920e10623010.15252/embj.202010623032876341
    [Google Scholar]
  62. EberleR.J. CoronadoM.A. GeringI. SommerhageS. KorostovK. StefanskiA. StühlerK. Kraemer-SchulienV. BlömekeL. BannachO. WillboldD. Tau protein aggregation associated with SARS-COV-2 main protease.PLoS One2023188e028813810.1371/journal.pone.028813837603556
    [Google Scholar]
  63. ZhangJ. MesiasV.S.D. ChesneyA.D. AnandV.K. FengX. HsingI.M. HansmannU.H.E. HuangJ. Differential effects of SARS-COV-2 amyloidogenic segments on the aggregation and toxicity of human islet amyloid polypeptide within membrane environments.Int. J. Biol. Macromol.2024283Pt 413793010.1016/j.ijbiomac.2024.13793039579816
    [Google Scholar]
  64. GhoshA. PithadiaA.S. BhatJ. BeraS. MidyaA. FierkeC.A. RamamoorthyA. BhuniaA. Self-assembly of a nine-residue amyloid-forming peptide fragment of SARS corona virus E-protein: Mechanism of self aggregation and amyloid-inhibition of hIAPP.Biochemistry201554132249226110.1021/acs.biochem.5b0006125785896
    [Google Scholar]
  65. SinghA.K. KhuntiK. COVID-19 and diabetes.Annu. Rev. Med.202273112914710.1146/annurev‑med‑042220‑01185734379444
    [Google Scholar]
  66. ZilioG. MasatoA. SandreM. CaregnatoA. MoretF. MaciolaA.K. AntoniniA. BrucaleM. CendronL. PlotegherN. BubaccoL. SARS-COV-2-mimicking pseudoviral particles accelerate α-synuclein aggregation in vitro.ACS Chem. Neurosci.202415221522110.1021/acschemneuro.3c0046838131609
    [Google Scholar]
  67. MesiasV.S.D. ZhuH. TangX. DaiX. LiuW. GuoY. HuangJ. Moderate binding between two SARS-COV-2 protein segments and α-synuclein alters its toxic oligomerization propensity differently.J. Phys. Chem. Lett.20221345106421064810.1021/acs.jpclett.2c0227836354180
    [Google Scholar]
  68. WangJ. DaiL. DengM. XiaoT. ZhangZ. ZhangZ. SARS-COV-2 spike protein s1 domain accelerates α-synuclein phosphorylation and aggregation in cellular models of synucleinopathy.Mol. Neurobiol.20246142446245810.1007/s12035‑023‑03726‑937897633
    [Google Scholar]
  69. MaG. ZhangD.F. ZouQ.C. XieX. XuL. FengX.L. LiX. HanJ.B. YuD. DengZ.H. QuW. LongJ. LiM.H. YaoY.G. ZengJ. SARS-COV-2 Spike protein S2 subunit modulates γ-secretase and enhances amyloid-β production in COVID-19 neuropathy.Cell Discov.2022819910.1038/s41421‑022‑00458‑336180433
    [Google Scholar]
  70. WangY. MandelkowE. Tau in physiology and pathology.Nat. Rev. Neurosci.2016171223510.1038/nrn.2015.126631930
    [Google Scholar]
  71. YangJ. LiY. WangS. LiH. ZhangL. ZhangH. WangP.H. ZhengX. YuX.F. WeiW. The SARS-COV-2 main protease induces neurotoxic TDP-43 cleavage and aggregates.Signal Transduct. Target. Ther.20238110910.1038/s41392‑023‑01386‑836894543
    [Google Scholar]
  72. JoM. LeeS. JeonY.M. KimS. KwonY. KimH.J. The role of TDP-43 propagation in neurodegenerative diseases: Integrating insights from clinical and experimental studies.Exp. Mol. Med.202052101652166210.1038/s12276‑020‑00513‑733051572
    [Google Scholar]
  73. ArseniD. ChenR. MurzinA.G. Peak-ChewS.Y. GarringerH.J. NewellK.L. KametaniF. RobinsonA.C. VidalR. GhettiB. HasegawaM. Ryskeldi-FalconB. TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP.Nature2023620797589890310.1038/s41586‑023‑06405‑w37532939
    [Google Scholar]
  74. AlbornozE.A. AmarillaA.A. ModhiranN. ParkerS. LiX.X. WijesundaraD.K. AguadoJ. ZamoraA.P. McMillanC.L.D. LiangB. PengN.Y.G. SngJ.D.J. SaimaF.T. FungJ.N. LeeJ.D. ParamithaD. ParryR. AvumegahM.S. IsaacsA. LoM.W. Miranda-ChaconZ. BradshawD. Salinas-RebolledoC. RajapakseN.W. WolvetangE.J. MunroT.P. Rojas-FernandezA. YoungP.R. StaceyK.J. KhromykhA.A. ChappellK.J. WattersonD. WoodruffT.M. SARS-COV-2 drives NLRP3 inflammasome activation in human microglia through spike protein.Mol. Psychiatry20232872878289310.1038/s41380‑022‑01831‑036316366
    [Google Scholar]
  75. GordonR. AlbornozE.A. ChristieD.C. LangleyM.R. KumarV. MantovaniS. RobertsonA.A.B. ButlerM.S. RoweD.B. O’NeillL.A. KanthasamyA.G. SchroderK. CooperM.A. WoodruffT.M. Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice.Sci. Transl. Med.201810465eaah406610.1126/scitranslmed.aah406630381407
    [Google Scholar]
  76. ChangM.H. ParkJ.H. LeeH.K. ChoiJ.Y. KohY.H. SARS-COV-2 spike protein 1 causes aggregation of α-synuclein via microglia-induced inflammation and production of mitochondrial ROS: Potential therapeutic applications of metformin.Biomedicines2024126122310.3390/biomedicines1206122338927430
    [Google Scholar]
  77. PanP. ShenM. YuZ. GeW. ChenK. TianM. XiaoF. WangZ. WangJ. JiaY. WangW. WanP. ZhangJ. ChenW. LeiZ. ChenX. LuoZ. ZhangQ. XuM. LiG. LiY. WuJ. SARS-COV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.Nat. Commun.2021121466410.1038/s41467‑021‑25015‑634341353
    [Google Scholar]
  78. ChiricostaL. GugliandoloA. MazzonE. SARS-COV-2 exacerbates beta-amyloid neurotoxicity, inflammation and oxidative stress in Alzheimer’s disease patients.Int. J. Mol. Sci.202122241360310.3390/ijms22241360334948400
    [Google Scholar]
  79. LeeB. ChoiH.N. CheY.H. KoM. SeongH.M. JoM.G. KimS.H. SongC. YoonS. ChoiJ. KimJ.H. KimM. LeeM.Y. ParkS.W. KimH.J. KimS.J. MoonD.S. LeeS. ParkJ.H. YeoS.G. EversonR.G. KimY.J. HongK.W. RohI.S. LyooK.S. KimY.J. YunS.P. SARS-COV-2 infection exacerbates the cellular pathology of Parkinson’s disease in human dopaminergic neurons and a mouse model.Cell Rep. Med.20245510157010.1016/j.xcrm.2024.10157038749422
    [Google Scholar]
  80. GainC. SongS. AngtuacoT. SattaS. KelesidisT. The role of oxidative stress in the pathogenesis of infections with coronaviruses.Front. Microbiol.202313111193010.3389/fmicb.2022.111193036713204
    [Google Scholar]
  81. DeyR. BishayiB. Microglial inflammatory responses to sars-cov-2 infection: A comprehensive review.Cell. Mol. Neurobiol.2024441210.1007/s10571‑023‑01444‑338099973
    [Google Scholar]
  82. PomilioA.B. VitaleA.A. LazarowskiA.J. COVID-19 and alzheimer’s disease: Neuroinflammation, oxidative stress, ferroptosis, and mechanisms involved.Curr. Med. Chem.202330353993403110.2174/092986732966622100310154836200215
    [Google Scholar]
  83. HamadR.S. Al-kuraishyH.M. AlexiouA. PapadakisM. AhmedE.A. SaadH.M. BatihaG.E.S. SARS-COV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway.Cell Stre. Chap.202328665767310.1007/s12192‑023‑01379‑037796433
    [Google Scholar]
  84. ChesneyA.D. MaitiB. HansmannU.H.E. Human amylin in the presence of SARS-COV-2 protein fragments.ACS Omega2023813125011251110.1021/acsomega.3c0062137033831
    [Google Scholar]
  85. ChesneyA.D. MaitiB. HansmannU.H.E. SARS-COV-2 spike protein fragment eases amyloidogenesis of α-synuclein.J. Chem. Phys.2023159101510310.1063/5.015733137409768
    [Google Scholar]
  86. CoppolaF. PavlíčekT. KrálP. Coupling of SARS-COV-2 to Aβ amyloid fibrils.ACS Omega2024989295929910.1021/acsomega.3c0848138434865
    [Google Scholar]
  87. IdreesD. KumarV. SARS-COV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration.Biochem. Biophys. Res. Commun.2021554949810.1016/j.bbrc.2021.03.10033789211
    [Google Scholar]
  88. Flores-LeónM. LázaroD.F. ShvachiyL. KriskoA. OuteiroT.F. In silico analysis of the aggregation propensity of the SARS-COV-2 proteome: Insight into possible cellular pathologies.Biochim. Biophys. Acta. Prot. Prot.202118691014069310.1016/j.bbapap.2021.14069334237472
    [Google Scholar]
  89. Ribeiro-FilhoH.V. JaraG.E. BatistaF.A.H. SchlederG.R. TonoliC.C.C. SopranoA.S. GuimarãesS.L. BorgesA.C. CassagoA. BajgelmanM.C. MarquesR.E. TrivellaD.B.B. FranchiniK.G. FigueiraA.C.M. BenedettiC.E. Lopes-de-OliveiraP.S. Structural dynamics of SARS-COV-2 nucleocapsid protein induced by RNA binding.PLOS Comput. Biol.2022185e101012110.1371/journal.pcbi.101012135551296
    [Google Scholar]
  90. CarusoI.P. dos Santos AlmeidaV. AmaralD.M.J. AndradeD.G.C. AraújoD.G.R. AraújoD.T.S. AzevedoD.J.M. BarbosaG.M. BartkevihiL. BezerraP.R. dos Santos CabralK.M. LourençoD.I.O. Malizia-MottaC.L.F. MarquesL.D.A. Mebus-AntunesN.C. Neves-MartinsT.C. SáD.J.M. SanchesK. Santana-SilvaM.C. VasconcelosA.A. da Silva AlmeidaM. AmorimD.G.C. AnobomC.D. PoianD.A.T. Gomes-NetoF. PinheiroA.S. AlmeidaF.C.L. Insights into the specificity for the interaction of the promiscuous SARS-COV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids.Int. J. Biol. Macromol.202220346648010.1016/j.ijbiomac.2022.01.12135077748
    [Google Scholar]
  91. CarusoÍ.P. SanchesK. PoianD.A.T. PinheiroA.S. AlmeidaF.C.L. Dynamics of the SARS-COV-2 nucleoprotein N-terminal domain triggers RNA duplex destabilization.Biophys. J.2021120142814282710.1016/j.bpj.2021.06.00334197802
    [Google Scholar]
  92. KhanA. KhanT.M. SaleemS. JunaidM. AliA. AliS.S. KhanM. WeiD.Q. Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-COV-2 nucleocapsid phosphoprotein.Comput. Struct. Biotechnol. J.2020182174218410.1016/j.csbj.2020.08.00632837710
    [Google Scholar]
  93. SankararamanS. HamreJ.III AlmsnedF. AljouieA. BokhariY. AlawwadM. AlomairL. JafriM.S. Active site prediction of phosphorylated SARS-COV-2 N-Protein using molecular simulation.Inform. Med. Unlock.20222910088910.1016/j.imu.2022.10088935224174
    [Google Scholar]
  94. MuradyanN. ArakelovV. SargsyanA. ParonyanA. ArakelovG. NazaryanK. Impact of mutations on the stability of SARS-COV-2 nucleocapsid protein structure.Sci. Rep.2024141587010.1038/s41598‑024‑55157‑838467657
    [Google Scholar]
  95. RóżyckiB. BouraE. Conformational ensemble of the full-length SARS-COV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data.Biophys. Chem.202228810684310.1016/j.bpc.2022.10684335696898
    [Google Scholar]
  96. GotorN.L. ArmaosA. CalloniG. BurgasT.M. VabulasR.M. GrootD.N.S. TartagliaG.G. RNA-binding and prion domains: The Yin and Yang of phase separation.Nucleic Acids Res.202048179491950410.1093/nar/gkaa68132857852
    [Google Scholar]
  97. RayS. SinghN. KumarR. PatelK. PandeyS. DattaD. MahatoJ. PanigrahiR. NavalkarA. MehraS. GadheL. ChatterjeeD. SawnerA.S. MaitiS. BhatiaS. GerezJ.A. ChowdhuryA. KumarA. PadinhateeriR. RiekR. KrishnamoorthyG. MajiS.K. α-Synuclein aggregation nucleates through liquid–liquid phase separation.Nat. Chem.202012870571610.1038/s41557‑020‑0465‑932514159
    [Google Scholar]
  98. RaiS.K. SavastanoA. SinghP. MukhopadhyayS. ZweckstetterM. Liquid–liquid phase separation of tau: From molecular biophysics to physiology and disease.Protein Sci.20213071294131410.1002/pro.409333930220
    [Google Scholar]
  99. CarterG.C. HsiungC.H. SimpsonL. YangH. ZhangX. N-terminal domain of TDP43 enhances liquid-liquid phase separation of globular proteins.J. Mol. Biol.20214331016694810.1016/j.jmb.2021.16694833744316
    [Google Scholar]
  100. LuS. YeQ. SinghD. CaoY. DiedrichJ.K. YatesJ.R.III VillaE. ClevelandD.W. CorbettK.D. The SARS-COV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein.Nat. Commun.202112150210.1038/s41467‑020‑20768‑y33479198
    [Google Scholar]
  101. CasasantaM.A. JonaidG.M. KaylorL. LuqiuW.Y. DiCeccoL.A. SolaresM.J. BerryS. DearnaleyW.J. KellyD.F. Retracted: Structural insights of the SARS-COV-2 nucleocapsid protein: Implications for the inner-workings of rapid antigen tests.Microsc. Microanal.202329264965710.1093/micmic/ozac03637749713
    [Google Scholar]
  102. JackA. FerroL.S. TrnkaM.J. WehriE. NadgirA. NguyenlaX. FoxD. CostaK. StanleyS. SchaletzkyJ. YildizA. SARS-COV-2 nucleocapsid protein forms condensates with viral genomic RNA.PLoS Biol.20211910e300142510.1371/journal.pbio.300142534634033
    [Google Scholar]
  103. CarlsonC.R. AsfahaJ.B. GhentC.M. HowardC.J. HartooniN. SafariM. FrankelA.D. MorganD.O. Phosphoregulation of phase separation by the SARS-COV-2 n protein suggests a biophysical basis for its dual functions.Mol. Cell202080610921103.e410.1016/j.molcel.2020.11.02533248025
    [Google Scholar]
  104. SandersD.W. KedershaN. LeeD.S.W. StromA.R. DrakeV. RibackJ.A. BrachaD. EeftensJ.M. IwanickiA. WangA. WeiM.T. WhitneyG. LyonsS.M. AndersonP. JacobsW.M. IvanovP. BrangwynneC.P. Competing protein-RNA interaction networks control multiphase intracellular organization.Cell20201812306324.e2810.1016/j.cell.2020.03.05032302570
    [Google Scholar]
  105. GaoT. GaoY. LiuX. NieZ. SunH. LinK. PengH. WangS. Identification and functional analysis of the SARS-COV-2 nucleocapsid protein.BMC Microbiol.20212115810.1186/s12866‑021‑02107‑333618668
    [Google Scholar]
  106. ZhouR. ZengR. BrunnV.A. LeiJ. Structural characterization of the C-terminal domain of SARS-COV-2 nucleocapsid protein.Mol. Biomed.202011210.1186/s43556‑020‑00001‑434765991
    [Google Scholar]
  107. WangS. DaiT. QinZ. PanT. ChuF. LouL. ZhangL. YangB. HuangH. LuH. ZhouF. Targeting liquid–liquid phase separation of SARS-COV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity.Nat. Cell Biol.202123771873210.1038/s41556‑021‑00710‑034239064
    [Google Scholar]
  108. WuC. QaviA.J. HachimA. KavianN. ColeA.R. MoyleA.B. WagnerN.D. Sweeney-GibbonsJ. RohrsH.W. GrossM.L. PeirisJ.S.M. BaslerC.F. FarnsworthC.W. ValkenburgS.A. AmarasingheG.K. LeungD.W. Characterization of SARS-COV-2 nucleocapsid protein reveals multiple functional consequences of the C-terminal domain.iScience202124610268110.1016/j.isci.2021.10268134095780
    [Google Scholar]
  109. CubukJ. AlstonJ.J. InciccoJ.J. HolehouseA.S. HallK.B. Stuchell-BreretonM.D. SorannoA. The disordered N-terminal tail of SARS-COV-2 Nucleocapsid protein forms a dynamic complex with RNA.Nucleic Acids Res.20245252609262410.1093/nar/gkad121538153183
    [Google Scholar]
  110. DhamotharanK. KornS.M. WackerA. BeckerM.A. GüntherS. SchwalbeH. SchlundtA. A core network in the SARS-COV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding.Nat. Commun.20241511065610.1038/s41467‑024‑55024‑039653699
    [Google Scholar]
  111. CascarinaS.M. RossE.D. Phase separation by the SARS-COV-2 nucleocapsid protein: Consensus and open questions.J. Biol. Chem.2022298310167710.1016/j.jbc.2022.10167735131265
    [Google Scholar]
  112. ZengW. LiuG. MaH. ZhaoD. YangY. LiuM. MohammedA. ZhaoC. YangY. XieJ. DingC. MaX. WengJ. GaoY. HeH. JinT. Biochemical characterization of SARS-COV-2 nucleocapsid protein.Biochem. Biophys. Res. Commun.2020527361862310.1016/j.bbrc.2020.04.13632416961
    [Google Scholar]
  113. IsermanC. RodenC.A. BoernekeM.A. SealfonR.S.G. McLaughlinG.A. JungreisI. FritchE.J. HouY.J. EkenaJ. WeidmannC.A. TheesfeldC.L. KellisM. TroyanskayaO.G. BaricR.S. SheahanT.P. WeeksK.M. GladfelterA.S. Genomic RNA elements drive phase separation of the SARS-COV-2 nucleocapsid.Mol. Cell202080610781091.e610.1016/j.molcel.2020.11.04133290746
    [Google Scholar]
  114. YaronT.M. HeatonB.E. LevyT.M. JohnsonJ.L. JordanT.X. CohenB.M. KerelskyA. LinT.Y. LiberatoreK.M. BulaonD.K. NestV.S.J. KoundourosN. KastenhuberE.R. MercadanteM.N. Shobana-GaneshK. HeL. SchwartzR.E. ChenS. WeinsteinH. ElementoO. PiskounovaE. Nilsson- PayantB.E. LeeG. TrimarcoJ.D. BurkeK.N. HameleC.E. ChaparianR.R. HardingA.T. TataA. ZhuX. TataP.R. SmithC.M. PossematoA.P. TkachevS.L. HornbeckP.V. BeausoleilS.A. AnandS.K. AguetF. GetzG. DavidsonA.D. HeesomK. Kavanagh-WilliamsonM. MatthewsD.A. tenOeverB.R. CantleyL.C. BlenisJ. HeatonN.S. Host protein kinases required for SARS-COV-2 nucleocapsid phosphorylation and viral replication.Sci. Signal.202215757eabm080810.1126/scisignal.abm080836282911
    [Google Scholar]
  115. BotovaM. Camacho-ZarcoA.R. TognettiJ. BessaL.M. GusevaS. MikkolaE. SalviN. MaurinD. HerrmannT. BlackledgeM. A specific phosphorylation-dependent conformational switch in SARS-COV-2 nucleocapsid protein inhibits RNA binding.Sci. Adv.20241031eaax232310.1126/sciadv.aax232339093972
    [Google Scholar]
  116. StuweH. ReardonP.N. YuZ. ShahS. HughesK. BarbarE.J. Phosphorylation in the Ser/Arg-rich region of the nucleocapsid of SARS-COV-2 regulates phase separation by inhibiting self-association of a distant helix.J. Biol. Chem.2024300610735410.1016/j.jbc.2024.10735438718862
    [Google Scholar]
  117. ChenA. LupanA.M. QuekR.T. StanciuS.G. AsafteiM. StanciuG.A. HardyK.S. MagalhãesA.D.T. SilverP.A. MitchisonT.J. SalicA. A coronaviral pore-replicase complex links RNA synthesis and export from double-membrane vesicles.Sci. Adv.20241045eadq958010.1126/sciadv.adq958039514670
    [Google Scholar]
  118. ZimmermannL. ZhaoX. MakroczyovaJ. Wachsmuth-MelmM. PrasadV. HenselZ. BartenschlagerR. ChlandaP. SARS-COV-2 NSP3 and NSP4 are minimal constituents of a pore spanning replication organelle.Nat. Commun.2023141789410.1038/s41467‑023‑43666‑538036567
    [Google Scholar]
  119. HuangY. WangT. ZhongL. ZhangW. ZhangY. YuX. YuanS. NiT. Molecular architecture of coronavirus double-membrane vesicle pore complex.Nature2024633802822423110.1038/s41586‑024‑07817‑y39143215
    [Google Scholar]
  120. NiX. HanY. ZhouR. ZhouY. LeiJ. Structural insights into ribonucleoprotein dissociation by nucleocapsid protein interacting with non-structural protein 3 in SARS-COV-2.Commun. Biol.20236119310.1038/s42003‑023‑04570‑236806252
    [Google Scholar]
  121. BessaL.M. GusevaS. Camacho-ZarcoA.R. SalviN. MaurinD. PerezL.M. BotovaM. MalkiA. NanaoM. JensenM.R. RuigrokR.W.H. BlackledgeM. The intrinsically disordered SARS-COV-2 nucleoprotein in dynamic complex with its viral partner NSP3a.Sci. Adv.202283eabm403410.1126/sciadv.abm403435044811
    [Google Scholar]
  122. RoingeardP. EymieuxS. Burlaud-GaillardJ. HouriouxC. PatientR. BlanchardE. The double-membrane vesicle (DMV): A virus-induced organelle dedicated to the replication of SARS-COV-2 and other positive-sense single-stranded RNA viruses.Cell. Mol. Life Sci.202279842510.1007/s00018‑022‑04469‑x35841484
    [Google Scholar]
  123. WolffG. LimpensR.W.A.L. Zevenhoven-DobbeJ.C. LaugksU. ZhengS. JongD.A.W.M. KoningR.I. AgardD.A. GrünewaldK. KosterA.J. SnijderE.J. BárcenaM. A molecular pore spans the double membrane of the coronavirus replication organelle.Science202036965091395139810.1126/science.abd362932763915
    [Google Scholar]
  124. SavastanoA. Ibáñez de OpakuaA. RankovicM. ZweckstetterM. Nucleocapsid protein of SARS-COV-2 phase separates into RNA-rich polymerase-containing condensates.Nat. Commun.2020111604110.1038/s41467‑020‑19843‑133247108
    [Google Scholar]
  125. SnijderE.J. LimpensR.W.A.L. WildeD.A.H. JongD.A.W.M. Zevenhoven-DobbeJ.C. MaierH.J. FaasF.F.G.A. KosterA.J. BárcenaM. A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis.PLoS Biol.2020186e300071510.1371/journal.pbio.300071532511245
    [Google Scholar]
  126. NikolicJ. BarsL.R. LamaZ. ScrimaN. Lagaudrière-GesbertC. GaudinY. BlondelD. Negri bodies are viral factories with properties of liquid organelles.Nat. Commun.2017815810.1038/s41467‑017‑00102‑928680096
    [Google Scholar]
  127. WuH. XingN. MengK. FuB. XueW. DongP. TangW. XiaoY. LiuG. LuoH. Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-COV-2.Cell. Host. Microbe.2021291217881801.e610.1016/j.chom.2021.11.005
    [Google Scholar]
  128. AdlyA.N. BiM. CarlsonC.R. SyedA.M. CilingA. DoudnaJ.A. ChengY. MorganD.O. Assembly of SARS-COV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein.J. Biol. Chem.20232991210536210.1016/j.jbc.2023.10536237863261
    [Google Scholar]
  129. MourierT. ShuaibM. HalaS. MfarrejS. AlofiF. NaeemR. AlsomaliA. JorgensenD. SubudhiA.K. RachedB.F. GuanQ. SalunkeR.P. OoiA. EsauL. DouvropoulouO. NugmanovaR. PerumalS. ZhangH. RajanI. Al-OmariA. SalihS. ShamsanA. MutairA.A. TahaJ. AlahmadiA. KhotaniN. AlhamssA. MahmoudA. AlquthamiK. DageegA. KhogeerA. HashemA.M. MoragaP. VolzE. AlmontashiriN. PainA. SARS-COV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.Nat. Commun.202213160110.1038/s41467‑022‑28287‑835105893
    [Google Scholar]
  130. ZhaoH. WuD. HassanS.A. NguyenA. ChenJ. PiszczekG. SchuckP. A conserved oligomerization domain in the disordered linker of coronavirus nucleocapsid proteins.Sci. Adv.2023914eadg647310.1126/sciadv.adg647337018390
    [Google Scholar]
  131. JohnsonB.A. ZhouY. LokugamageK.G. VuM.N. BoppN. Crocquet-ValdesP.A. KalveramB. SchindewolfC. LiuY. SchartonD. PlanteJ.A. XieX. AguilarP. WeaverS.C. ShiP.Y. WalkerD.H. RouthA.L. PlanteK.S. MenacheryV.D. Nucleocapsid mutations in SARS-COV-2 augment replication and pathogenesis.PLoS Pathog.2022186e101062710.1371/journal.ppat.101062735728038
    [Google Scholar]
  132. CarlsonC.R. AdlyA.N. BiM. HowardC.J. FrostA. ChengY. MorganD.O. Reconstitution of the SARS-COV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation.J. Biol. Chem.20222981110256010.1016/j.jbc.2022.10256036202211
    [Google Scholar]
  133. KleinS. CorteseM. WinterS.L. Wachsmuth-MelmM. NeufeldtC.J. CerikanB. StaniferM.L. BoulantS. BartenschlagerR. ChlandaP. SARS-COV-2 structure and replication characterized by in situ cryo-electron tomography.Nat. Commun.2020111588510.1038/s41467‑020‑19619‑733208793
    [Google Scholar]
  134. SunZ. WangM. WangW. LiD. WangJ. SuiG. Getah virus capsid protein undergoes co-condensation with viral genomic RNA to facilitate virion assembly.Int. J. Biol. Macromol.2024265Pt 113084710.1016/j.ijbiomac.2024.13084738490381
    [Google Scholar]
  135. KumarP. KumarA. GargN. GiriR. An insight into SARS-COV-2 membrane protein interaction with spike, envelope, and nucleocapsid proteins.J. Biomol. Struct. Dyn.20234131062107110.1080/07391102.2021.201649034913847
    [Google Scholar]
  136. NguyenH. NguyenH.L. LanP.D. ThaiN.Q. SikoraM. LiM.S. Interaction of SARS-COV-2 with host cells and antibodies: Experiment and simulation.Chem. Soc. Rev.202352186497655310.1039/D1CS01170G37650302
    [Google Scholar]
  137. Al-AlyZ. DavisH. McCorkellL. SoaresL. Wulf-HansonS. IwasakiA. TopolE.J. Long COVID science, research and policy.Nat. Med.20243082148216410.1038/s41591‑024‑03173‑639122965
    [Google Scholar]
  138. HuangC. FengF. ShiY. LiW. WangZ. ZhuY. YuanS. HuD. DaiJ. JiangQ. ZhangR. LiuC. ZhangP. Protein kinase C inhibitors reduce SARS-COV-2 replication in cultured cells.Microbiol. Spectr.2022105e01056-2210.1128/spectrum.01056‑2236000889
    [Google Scholar]
  139. GuoS. LeiX. ChangY. ZhaoJ. WangJ. DongX. LiuQ. ZhangZ. WangL. YiD. MaL. LiQ. ZhangY. DingJ. LiangC. LiX. GuoF. WangJ. CenS. SARS-COV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.Signal Transduct. Target. Ther.20227140010.1038/s41392‑022‑01239‑w36575184
    [Google Scholar]
  140. YaoH. SongY. ChenY. WuN. XuJ. SunC. ZhangJ. WengT. ZhangZ. WuZ. ChengL. ShiD. LuX. LeiJ. CrispinM. ShiY. LiL. LiS. Molecular architecture of the SARS-COV-2 virus.Cell20201833730738.e1310.1016/j.cell.2020.09.01832979942
    [Google Scholar]
/content/journals/cpps/10.2174/0113892037354482250414045355
Loading
/content/journals/cpps/10.2174/0113892037354482250414045355
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test