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SARS-CoV-2 nucleocapsid protein: Importance in viral infection

  • 1.

    Department of Obstetrics and Gynecology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China

  • 2.

    Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China

  • 3.

    Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore 53700, Pakistan

  • 4.

    Department of Infectious Diseases, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China

  • 5.

    CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China

Cite this:
https://doi.org/10.52396/JUSTC-2022-0020
More Information
  • Author Bio:

    H. M. Shifa ul Haq is currently a Ph.D. student at the University of Science and Technology of China. His research focuses on molecular mechanism of host-microbe interactions

    Hongliang He received his Ph.D. degree in Infectious Diseases from Sun Yat-sen University. He is a physician in Department of Infectious Diseases at the First Affiliated Hospital of USTC. His research interests include diagnosis, mechanism and treatment of infectious diseases

    Tengchuan Jin received his Ph.D. degree in Molecular Biochemistry and Biophysics from Illinois Institute of Technology. He is a professor at the Division of Life Sciences and Medicine, University of Science and Technology of China. His research interests include molecular mechanism of host-microbe interaction, therapeutic antibody development

  • Corresponding author: E-mail: hhl725@ustc.edu.cn; E-mail: jint@ustc.edu.cn
  • Received Date: 22 January 2022
  • Accepted Date: 02 April 2022
    Abstract

  • Abstract

    The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of deaths worldwide. Therefore, it is critical to understand the biological basis of SARS-CoV-2 to develop novel approaches to control its spread. The SARS-CoV-2 nucleocapsid (N) protein is an important diagnostic and potent therapeutic target of the disease, as it is involved in numerous important functions in the viral life cycle. Several studies have explained the structural and functional aspects of the SARS-CoV-2 N protein. This review summarizes the currently available data on the evolutionarily conserved N protein of SARS-CoV-2 by providing detailed information on the structural and multifunctional characteristics of the N protein.

    Graphical abstract

    Structure and functions of SARS-CoV-2 nucleocapsid protein.

    Abstract

    The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of deaths worldwide. Therefore, it is critical to understand the biological basis of SARS-CoV-2 to develop novel approaches to control its spread. The SARS-CoV-2 nucleocapsid (N) protein is an important diagnostic and potent therapeutic target of the disease, as it is involved in numerous important functions in the viral life cycle. Several studies have explained the structural and functional aspects of the SARS-CoV-2 N protein. This review summarizes the currently available data on the evolutionarily conserved N protein of SARS-CoV-2 by providing detailed information on the structural and multifunctional characteristics of the N protein.

    • Public Summary

    • SARS-CoV-2 nucleocapsid (N) protein is an important structural and multifunctional protein.
    • N protein of SARS-CoV-2 consists of five major domains including N terminal tail, N-NTD, LKR, N-CTD, and IDR.
    • N protein acts as a multifunctional protein by playing roles in genome packaging, RNA chaperoning, protein transport, DNA degradation, interfering with host translation, and limiting host immune responses.
    • N protein is an important target for T-cell activation and vaccine design.

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    • References(100)
  • [1]
    Bai Z H, Cao Y, Liu W G, et al. The SARS-CoV-2 nucleocapsid protein and its role in viral structure, biological functions, and a potential target for drug or vaccine mitigation. Viruses, 2021, 13 (6): 1115. doi: 10.3390/v13061115
    [2]
    Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579 (7798): 265–269. doi: 10.1038/s41586-020-2008-3
    [3]
    Zhu N, Zhang D Y, Wang W L, et al. A novel coronavirus from patients with pneumonia in China, 2019. The New England Journal of Medicine, 2020, 382 (8): 727–733. doi: 10.1056/NEJMoa2001017
    [4]
    Huang C L, Wang Y M, Li X W, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet, 2020, 395 (10223): 497–506. doi: 10.1016/S0140-6736(20)30183-5
    [5]
    Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus pandemic (COVID-19). https://ourworldindata.org/coronavirus.
    [6]
    Lurie N, Saville M, Hatchett R, et al. Developing COVID-19 vaccines at pandemic speed. The New England Journal of Medicine, 2020, 382 (21): 1969–1973. doi: 10.1056/NEJMp2005630
    [7]
    Cui J, Li F, Shi Z L. Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 2019, 17 (3): 181–192. doi: 10.1038/s41579-018-0118-9
    [8]
    Zhu G L, Zhu C M, Zhu Y, et al. Minireview of progress in the structural study of SARS-CoV-2 proteins. Current Research in Microbial Sciences, 2020, 1: 53–61. doi: 10.1016/j.crmicr.2020.06.003
    [9]
    Sola I, Almazán F, Zúñiga S, et al. Continuous and discontinuous RNA synthesis in coronaviruses. Annual Review of Virology, 2015, 2 (1): 265–288. doi: 10.1146/annurev-virology-100114-055218
    [10]
    Zheng Z Q, Wang S Y, Xu Z S, et al. SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication. Cell Discovery, 2021, 7 (1): 38. doi: 10.1038/s41421-021-00275-0
    [11]
    Lu R J, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The lancet, 2020, 395 (10224): 565–574. doi: 10.1016/S0140-6736(20)30251-8
    [12]
    Hassan S S, Choudhury P P, Roy B. SARS-CoV2 envelope protein: non-synonymous mutations and its consequences. Genomics, 2020, 112 (6): 3890–3892. doi: 10.1016/j.ygeno.2020.07.001
    [13]
    Snijder E J, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Advances in Virus Research, 2016, 96: 59–126. doi: 10.1016/bs.aivir.2016.08.008
    [14]
    Pasternak A O, Spaan W J M, Snijder E J. Nidovirus transcription: how to make sense…? Journal of General Virology, 2006, 87: 1403–1421. doi: 10.1099/vir.0.81611-0
    [15]
    Sawicki S G, Sawicki D L, Siddell S G. A contemporary view of coronavirus transcription. Journal of Virology, 2007, 81 (1): 20–29. doi: 10.1128/JVI.01358-06
    [16]
    Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579 (7798): 265–269. doi: 10.1038/s41586-020-2008-3
    [17]
    Ghosh S, Dellibovi-Ragheb T A, Kerviel A, et al. β-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway. Cell, 2020, 183 (6): 1520–1535.e14. doi: 10.1016/j.cell.2020.10.039
    [18]
    Shang B, Wang X Y, Yuan J W, et al. Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus. Biochemical and Biophysical Research Communications, 2005, 336 (1): 110–117. doi: 10.1016/j.bbrc.2005.08.032
    [19]
    Liu S J, Leng C H, Lien S P, et al. Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates. Vaccine, 2006, 24 (16): 3100–3108. doi: 10.1016/j.vaccine.2006.01.058
    [20]
    Atyeo C, Fischinger S, Zohar T, et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity, 2020, 53 (3): 524–532.e4. doi: 10.1016/j.immuni.2020.07.020
    [21]
    Syed A M, Taha T Y, Tabata T, et al. Rapid assessment of SARS-CoV-2-evolved variants using virus-like particles. Science, 2021, 374 (6575): 1626–1632. doi: 10.1126/science.abl6184
    [22]
    Khan A, Khan M T, Saleem S, et al. Structural Insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein. Computational and Structural Biotechnology Journal, 2020, 18: 2174–2184. doi: 10.1016/j.csbj.2020.08.006
    [23]
    Chen Y, Liu Q Y, Guo D Y. Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of Medical Virology, 2020, 92 (4): 418–423. doi: 10.1002/jmv.25681
    [24]
    Bar-On Y M, Flamholz A, Phillips R, et al. Science Forum: SARS-CoV-2 (COVID-19) by the numbers. eLife, 2020, 9: e57309. doi: 10.7554/eLife.57309
    [25]
    Narayanan K, Chen C J, Maeda J, et al. Nucleocapsid-independent specific viral RNA packaging via viral envelope protein and viral RNA signal. Journal of Virology, 2003, 77 (5): 2922–2927. doi: 10.1128/JVI.77.5.2922-2927.2003
    [26]
    Ahmed S F, Quadeer A A, McKay M R. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses, 2020, 12 (3): 254. doi: 10.3390/v12030254
    [27]
    Zhao H, Wu D, Nguyen A, et al. Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids. iScience, 2021, 24 (6): 102523. doi: 10.1016/j.isci.2021.102523
    [28]
    Tilocca B, Soggiu A, Sanguinetti M, et al. Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses. Microbes and Infection, 2020, 22: 188–194. doi: 10.1016/j.micinf.2020.04.002
    [29]
    Cubuk J, Alston J J, Incicco J J, et al. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nature Communications, 2021, 12 (1): 1936. doi: 10.1038/s41467-021-21953-3
    [30]
    Hurst K R, Koetzner C A, Masters P S. Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. Journal of Virology, 2009, 83 (14): 7221–7234. doi: 10.1128/JVI.00440-09
    [31]
    Fang H J, Chen Y Z, Li M S, et al. Thermostability of the N-terminal RNA-binding domain of the SARS-CoV nucleocapsid protein: Experiments and numerical simulations. Biophysical Journal, 2009, 96 (5): 1892–1901. doi: 10.1016/j.bpj.2008.10.045
    [32]
    Yang M, He S H, Chen X X, et al. Structural insight into the SARS-CoV-2 nucleocapsid protein C-terminal domain reveals a novel recognition mechanism for viral transcriptional regulatory sequences. Frontiers in Chemistry, 2021, 8: 624765. doi: 10.3389/fchem.2020.624765
    [33]
    Saikatendu K S, Joseph J S, Subramanian V, et al. Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein. Journal of Virology, 2007, 81 (8): 3913–3921. doi: 10.1128/JVI.02236-06
    [34]
    Chen C Y, Chang C K, Chang Y W, et al. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA. Journal of Molecular Biology, 2007, 368 (4): 1075–1086. doi: 10.1016/j.jmb.2007.02.069
    [35]
    Chang C K, Chen C M, Chiang M H, et al. Transient oligomerization of the SARS-CoV N protein–implication for virus ribonucleoprotein packaging. PloS One, 2013, 8 (5): e65045. doi: 10.1371/journal.pone.0065045
    [36]
    Jia Z H, Liu C, Chen Y W, et al. Crystal structures of the SARS-CoV-2 nucleocapsid protein C-terminal domain and development of nucleocapsid-targeting nanobodies. The FEBS Journal, 2021. https://doi.org/10.1111/febs.16239.
    [37]
    de Wit E, van Doremalen N, Falzarano D, et al. SARS and MERS: recent insights into emerging coronaviruses. Nature Reviews Microbiology, 2016, 14 (8): 523–534. doi: 10.1038/nrmicro.2016.81
    [38]
    Zhou P, Yang X L, Wang X G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579 (7798): 270–273. doi: 10.1038/s41586-020-2012-7
    [39]
    Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Research, 2014, 42 (W1): W320–W324. doi: 10.1093/nar/gku316
    [40]
    Sievers F, Wilm A, Dineen D, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular Systems Biology, 2011, 7 (1): 539. doi: 10.1038/msb.2011.75
    [41]
    Gao T Y, Gao Y D, Liu X X, et al. Identification and functional analysis of the SARS-COV-2 nucleocapsid protein. BMC Microbiology, 2021, 21 (1): 58. doi: 10.1186/s12866-021-02107-3
    [42]
    Zeng W H, Liu G F, Ma H, et al. Biochemical characterization of SARS-CoV-2 nucleocapsid protein. Biochemical and Biophysical Research Communications, 2020, 527 (3): 618–623. doi: 10.1016/j.bbrc.2020.04.136
    [43]
    Hiscox J A, Wurm T, Wilson L, et al. The coronavirus infectious bronchitis virus nucleoprotein localizes to the nucleolus. Journal of Virology, 2001, 75 (1): 506–512. doi: 10.1128/JVI.75.1.506-512.2001
    [44]
    Peng Y, Du N, Lei Y Q, et al. Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design. The EMBO Journal, 2020, 39 (20): e105938. doi: 10.15252/embj.2020105938
    [45]
    Prasad K, Ahamad S, Kanipakam H, et al. Simultaneous inhibition of SARS-CoV-2 entry pathways by cyclosporine. ACS Chemical Neuroscience, 2021, 12 (5): 930–944. doi: 10.1021/acschemneuro.1c00019
    [46]
    Caruso Í P, Sanches K, Da Poian A T, et al. Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism. BioRxiv, 2020. https://doi.org/10.1101/2020.08.24.264465.
    [47]
    Kang S S, Yang M, Hong Z S, et al. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites. Acta Pharmaceutica Sinica B, 2020, 10 (7): 1228–1238. doi: 10.1016/j.apsb.2020.04.009
    [48]
    Fehr A R, Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods in Molecular Biology (Clifton, N. J. ), 2015, 1282: 1–23. doi: 10.1007/978-1-4939-2438-7_1
    [49]
    Cui L, Wang H Y, Ji Y X, et al. The nucleocapsid protein of coronaviruses acts as a viral suppressor of RNA silencing in mammalian cells. Journal of Virology, 2015, 89 (17): 9029–9043. doi: 10.1128/JVI.01331-15
    [50]
    Chang C K, Hsu Y L, Chang Y H, et al. Multiple nucleic acid binding sites and intrinsic disorder of severe acute respiratory syndrome coronavirus nucleocapsid protein: Implications for ribonucleocapsid protein packaging. Journal of Virology, 2009, 83 (5): 2255–2264. doi: 10.1128/JVI.02001-08
    [51]
    de Haan C A, Rottier P J. Molecular interactions in the assembly of coronaviruses. Advances in Virus Research, 2005, 64: 165–230. doi: 10.1016/S0065-3527(05)64006-7
    [52]
    Robbins S G, Frana M F, McGowan J J, et al. RNA-binding proteins of coronavirus MHV: detection of monomeric and multimeric N protein with an RNA overlay-protein blot assay. Virology, 1986, 150 (2): 402–410. doi: 10.1016/0042-6822(86)90305-3
    [53]
    Baric R S, Nelson G W, Fleming J O, et al. Interactions between coronavirus nucleocapsid protein and viral RNAs: implications for viral transcription. Journal of Virology, 1988, 62 (11): 4280–4287. doi: 10.1128/jvi.62.11.4280-4287.1988
    [54]
    Cong Y, Ulasli M, Schepers H, et al. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle. Journal of Virology, 2020, 94 (4): e01925–19. doi: 10.1128/JVI.01925-19
    [55]
    Fan H, Ooi A, Tan Y W, et al. The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties. Structure, 2005, 13 (12): 1859–1868. doi: 10.1016/j.str.2005.08.021
    [56]
    Surjit M, Liu B, Kumar P, et al. The nucleocapsid protein of the SARS coronavirus is capable of self-association through a C-terminal 209 amino acid interaction domain. Biochemical and Biophysical Research Communications, 2004, 317 (4): 1030–1036. doi: 10.1016/j.bbrc.2004.03.154
    [57]
    Risco C, Antón I M, Enjuanes L, et al. The transmissible gastroenteritis coronavirus contains a spherical core shell consisting of M and N proteins. Journal of Virology, 1996, 70 (7): 4773–4777. doi: 10.1128/jvi.70.7.4773-4777.1996
    [58]
    Kuo L, Masters P S. Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. Journal of Virology, 2002, 76 (10): 4987–4999. doi: 10.1128/JVI.76.10.4987-4999.2002
    [59]
    Malone B, Urakova N, Snijder E J, et al. Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design. Nature Reviews Molecular Cell Biology, 2022, 23 (1): 21–39. doi: 10.1038/s41580-021-00432-z
    [60]
    Lo Y S, Lin S Y, Wang S M, et al. Oligomerization of the carboxyl terminal domain of the human coronavirus 229E nucleocapsid protein. FEBS Letters, 2013, 587 (2): 120–127. doi: 10.1016/j.febslet.2012.11.016
    [61]
    Grossoehme N E, Li L, Keane S C, et al. Coronavirus N protein N-terminal domain (NTD) specifically binds the transcriptional regulatory sequence (TRS) and melts TRS-cTRS RNA duplexes. Journal of Molecular Biology, 2009, 394 (3): 544–557. doi: 10.1016/j.jmb.2009.09.040
    [62]
    Gui M, Liu X, Guo D Y, et al. Electron microscopy studies of the coronavirus ribonucleoprotein complex. Protein & Cell, 2017, 8 (3): 219–224. doi: 10.1007/s13238-016-0352-8
    [63]
    Cong Y, Kriegenburg F, de Haan C A M, et al. Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers. Scientific Reports, 2017, 7 (1): 5740. doi: 10.1038/s41598-017-06062-w
    [64]
    Ma Y L, Tong X H, Xu X L, et al. Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus. Protein & Cell, 2010, 1 (7): 688–697. doi: 10.1007/s13238-010-0079-x
    [65]
    Kuo L, Hurst-Hess K R, Koetzner C A, et al. Analyses of coronavirus assembly interactions with interspecies membrane and nucleocapsid protein chimeras. Journal of Virology, 2016, 90 (9): 4357–4368. doi: 10.1128/JVI.03212-15
    [66]
    Shibabaw T, Molla M D, Teferi B, et al. Role of IFN and complements system: Innate immunity in SARS-CoV-2. Journal of Inflammation Research, 2020, 13: 507–518. doi: 10.2147/JIR.S267280
    [67]
    Amor S, Fernández Blanco L, Baker D. Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage. Clinical & Experimental Immunology, 2020, 202 (2): 193–209. doi: 10.1111/cei.13523
    [68]
    Ding S W, Han Q, Wang J, et al. Antiviral RNA interference in mammals. Current Opinion in Immunology, 2018, 54: 109–114. doi: 10.1016/j.coi.2018.06.010
    [69]
    Mu J, Xu J, Zhang L, et al. SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells. Science China Life Sciences, 2020, 63 (9): 1413–1416. doi: 10.1007/s11427-020-1692-1
    [70]
    Catanzaro M, Fagiani F, Racchi M, et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduction and Targeted Therapy, 2020, 5 (1): 84. doi: 10.1038/s41392-020-0191-1
    [71]
    Li J Y, Liao C H, Wang Q, et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Research, 2020, 286: 198074. doi: 10.1016/j.virusres.2020.198074
    [72]
    Zheng Y, Zhuang M W, Han L L, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling. Signal Transduction and Targeted Therapy, 2020, 5 (1): 299. doi: 10.1038/s41392-020-00438-7
    [73]
    Chen K L, Xiao F, Hu D W, et al. SARS-CoV-2 nucleocapsid protein interacts with RIG-I and represses RIG-mediated IFN-β production. Viruses, 2020, 13 (1): 47. doi: 10.3390/v13010047
    [74]
    Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 2020, 369 (6504): 718–724. doi: 10.1126/science.abc6027
    [75]
    Tian W M, Zhang N, Jin R H, et al. Immune suppression in the early stage of COVID-19 disease. Nature Communications, 2020, 11 (1): 5859. doi: 10.1038/s41467-020-19706-9
    [76]
    Zhao Y H, Sui L Y, Wu P, et al. A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response. Signal Transduction and Targeted Therapy, 2021, 6 (1): 331. doi: 10.1038/s41392-021-00742-w
    [77]
    Novoa R R, Calderita G, Arranz R, et al. Virus factories: associations of cell organelles for viral replication and morphogenesis. Biology of the Cell, 2005, 97 (2): 147–172. doi: 10.1042/BC20040058
    [78]
    Savastano A, Ibáñez de Opakua A, Rankovic M, et al. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nature Communications, 2020, 11 (1): 6041. doi: 10.1038/s41467-020-19843-1
    [79]
    Iserman C, Roden C A, Boerneke M A, et al. Genomic RNA elements drive phase separation of the SARS-CoV-2 nucleocapsid. Molecular Cell, 2020, 80 (6): 1078–1091.e6. doi: 10.1016/j.molcel.2020.11.041
    [80]
    Carlson C R, Asfaha J B, Ghent C M, et al. Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions. Molecular Cell, 2020, 80 (6): 1092–1103.e4. doi: 10.1016/j.molcel.2020.11.025
    [81]
    Chen H, Cui Y, Han X L, et al. Liquid–liquid phase separation by SARS-CoV-2 nucleocapsid protein and RNA. Cell Research, 2020, 30 (12): 1143–1145. doi: 10.1038/s41422-020-00408-2
    [82]
    Asselah T, Durantel D, Pasmant E, et al. COVID-19: Discovery, diagnostics and drug development. Journal of Hepatology, 2021, 74 (1): 168–184. doi: 10.1016/j.jhep.2020.09.031
    [83]
    Woloshin S, Patel N, Kesselheim A S. False negative tests for SARS-CoV-2 infection—challenges and implications. The New England Journal of Medicine, 2020, 383 (6): e38. doi: 10.1056/NEJMp2015897
    [84]
    Hartley G E, Edwards E S J, Aui P M, et al. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence. Science Immunology, 2020, 5 (54): eabf8891. doi: 10.1126/sciimmunol.abf8891
    [85]
    Li J, Lillehoj P B. Microfluidic magneto immunosensor for rapid, high sensitivity measurements of SARS-CoV-2 Nucleocapsid protein in serum. ACS Sensors, 2021, 6 (3): 1270–1278. doi: 10.1021/acssensors.0c02561
    [86]
    Amrun S N, Lee C Y, Lee B, et al. Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity. EBioMedicine, 2020, 58: 102911. doi: 10.1016/j.ebiom.2020.102911
    [87]
    Hachim A, Kavian N, Cohen C A, et al. Beyond the Spike: identification of viral targets of the antibody response to SARS-CoV-2 in COVID-19 patients. medRxiv, 2020. https://doi.org/10.1101/2020.04.30.20085670.
    [88]
    Zhang W, Du R H, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections, 2020, 9 (1): 386–389. doi: 10.1080/22221751.2020.1729071
    [89]
    Guo L, Ren L L, Yang S Y, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clinical Infectious Diseases, 2020, 71 (15): 778–785. doi: 10.1093/cid/ciaa310
    [90]
    Tomaras G D, Haynes B F. HIV-1-specific antibody responses during acute and chronic HIV-1 infection. Current Opinion in HIV and AIDS, 2009, 4 (5): 373–379. doi: 10.1097/COH.0b013e32832f00c0
    [91]
    Li T, Wang L, Wang H H, et al. Serum SARS-COV-2 nucleocapsid protein: A sensitivity and specificity early diagnostic marker for SARS-COV-2 infection. Frontiers in Cellular and Infection Microbiology, 2020, 10: 470. doi: 10.3389/fcimb.2020.00470
    [92]
    Lyu A H, Jin T C, Wang S S, et al. Automatic label-free immunoassay with high sensitivity for rapid detection of SARS-CoV-2 nucleocapsid protein based on chemiluminescent magnetic beads. Sensors and Actuators B:Chemical, 2021, 349: 130739. doi: 10.1016/j.snb.2021.130739
    [93]
    Wang S S, Shu J N, Lyu A H, et al. Label-free immunoassay for sensitive and rapid detection of the SARS-CoV-2 antigen based on functionalized magnetic nanobeads with chemiluminescence and immunoactivity. Analytical Chemistry, 2021, 93 (42): 14238–14246. doi: 10.1021/acs.analchem.1c03208
    [94]
    Wang Y T, Long X Y, Ding X, et al. Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2. European Journal of Medicinal Chemistry, 2022, 227: 113966. doi: 10.1016/j.ejmech.2021.113966
    [95]
    Lin S M, Lin S C, Hsu J N, et al. Structure-based stabilization of non-native protein–protein interactions of coronavirus nucleocapsid proteins in antiviral drug design. Journal of Medicinal Chemistry, 2020, 63 (6): 3131–3141. doi: 10.1021/acs.jmedchem.9b01913
    [96]
    Zhao M, Yu Y, Sun L M, et al. GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein. Nature Communications, 2021, 12 (1): 2114. doi: 10.1038/s41467-021-22297-8
    [97]
    Chen R E, Zhang X, Case J B, et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nature Medicine, 2021, 27 (4): 717–726. doi: 10.1038/s41591-021-01294-w
    [98]
    McBride R, van Zyl M, Fielding B C. The coronavirus nucleocapsid is a multifunctional protein. Viruses, 2014, 6 (8): 2991–3018. doi: 10.3390/v6082991
    [99]
    Sun B Q, Feng Y, Mo X N, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerging Microbes & Infections, 2020, 9 (1): 940–948. doi: 10.1080/22221751.2020.1762515
    [100]
    Qu J X, Wu C, Li X Y, et al. Profile of immunoglobulin G and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases, 2020, 71 (16): 2255–2258. doi: 10.1093/cid/ciaa489
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    Figure  1.  Structural model of SARS-CoV-2 N protein. Major structural domains of N protein with their sequence of amino acids in protein chain have been represented by different colors in the figure. The N-NTD and N-CTD are represented in green and purple, respectively. While IDR, LKR, and C terminal IDR are represented in brown, black, and blue, respectively.

    Figure  2.  Structural features and representation of SARS-CoV-2 N protein. (a) Structure of SARS-CoV-2 N protein[42]. The N-NTD and N-CTD are represented in green and purple, respectively. The other structural domain, including N-tail, NTD-CTD linker, and C-tail, are presented by brown, black, and blue, respectively. (b) Schematic representation of N-NTD of SARS-CoV-2 based on the SARS-CoV-2 N protein structure presented in (a). (c) Schematic representation of N-CTD of SARS-CoV-2 based on the SARS-CoV-2 N protein structure presented in (a). (b) and (c) are colored as in (a).

    [1]
    Bai Z H, Cao Y, Liu W G, et al. The SARS-CoV-2 nucleocapsid protein and its role in viral structure, biological functions, and a potential target for drug or vaccine mitigation. Viruses, 2021, 13 (6): 1115. doi: 10.3390/v13061115
    [2]
    Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579 (7798): 265–269. doi: 10.1038/s41586-020-2008-3
    [3]
    Zhu N, Zhang D Y, Wang W L, et al. A novel coronavirus from patients with pneumonia in China, 2019. The New England Journal of Medicine, 2020, 382 (8): 727–733. doi: 10.1056/NEJMoa2001017
    [4]
    Huang C L, Wang Y M, Li X W, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet, 2020, 395 (10223): 497–506. doi: 10.1016/S0140-6736(20)30183-5
    [5]
    Ritchie H, Mathieu E, Rodés-Guirao L, et al. Coronavirus pandemic (COVID-19). https://ourworldindata.org/coronavirus.
    [6]
    Lurie N, Saville M, Hatchett R, et al. Developing COVID-19 vaccines at pandemic speed. The New England Journal of Medicine, 2020, 382 (21): 1969–1973. doi: 10.1056/NEJMp2005630
    [7]
    Cui J, Li F, Shi Z L. Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 2019, 17 (3): 181–192. doi: 10.1038/s41579-018-0118-9
    [8]
    Zhu G L, Zhu C M, Zhu Y, et al. Minireview of progress in the structural study of SARS-CoV-2 proteins. Current Research in Microbial Sciences, 2020, 1: 53–61. doi: 10.1016/j.crmicr.2020.06.003
    [9]
    Sola I, Almazán F, Zúñiga S, et al. Continuous and discontinuous RNA synthesis in coronaviruses. Annual Review of Virology, 2015, 2 (1): 265–288. doi: 10.1146/annurev-virology-100114-055218
    [10]
    Zheng Z Q, Wang S Y, Xu Z S, et al. SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication. Cell Discovery, 2021, 7 (1): 38. doi: 10.1038/s41421-021-00275-0
    [11]
    Lu R J, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The lancet, 2020, 395 (10224): 565–574. doi: 10.1016/S0140-6736(20)30251-8
    [12]
    Hassan S S, Choudhury P P, Roy B. SARS-CoV2 envelope protein: non-synonymous mutations and its consequences. Genomics, 2020, 112 (6): 3890–3892. doi: 10.1016/j.ygeno.2020.07.001
    [13]
    Snijder E J, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Advances in Virus Research, 2016, 96: 59–126. doi: 10.1016/bs.aivir.2016.08.008
    [14]
    Pasternak A O, Spaan W J M, Snijder E J. Nidovirus transcription: how to make sense…? Journal of General Virology, 2006, 87: 1403–1421. doi: 10.1099/vir.0.81611-0
    [15]
    Sawicki S G, Sawicki D L, Siddell S G. A contemporary view of coronavirus transcription. Journal of Virology, 2007, 81 (1): 20–29. doi: 10.1128/JVI.01358-06
    [16]
    Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579 (7798): 265–269. doi: 10.1038/s41586-020-2008-3
    [17]
    Ghosh S, Dellibovi-Ragheb T A, Kerviel A, et al. β-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway. Cell, 2020, 183 (6): 1520–1535.e14. doi: 10.1016/j.cell.2020.10.039
    [18]
    Shang B, Wang X Y, Yuan J W, et al. Characterization and application of monoclonal antibodies against N protein of SARS-coronavirus. Biochemical and Biophysical Research Communications, 2005, 336 (1): 110–117. doi: 10.1016/j.bbrc.2005.08.032
    [19]
    Liu S J, Leng C H, Lien S P, et al. Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates. Vaccine, 2006, 24 (16): 3100–3108. doi: 10.1016/j.vaccine.2006.01.058
    [20]
    Atyeo C, Fischinger S, Zohar T, et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity, 2020, 53 (3): 524–532.e4. doi: 10.1016/j.immuni.2020.07.020
    [21]
    Syed A M, Taha T Y, Tabata T, et al. Rapid assessment of SARS-CoV-2-evolved variants using virus-like particles. Science, 2021, 374 (6575): 1626–1632. doi: 10.1126/science.abl6184
    [22]
    Khan A, Khan M T, Saleem S, et al. Structural Insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein. Computational and Structural Biotechnology Journal, 2020, 18: 2174–2184. doi: 10.1016/j.csbj.2020.08.006
    [23]
    Chen Y, Liu Q Y, Guo D Y. Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of Medical Virology, 2020, 92 (4): 418–423. doi: 10.1002/jmv.25681
    [24]
    Bar-On Y M, Flamholz A, Phillips R, et al. Science Forum: SARS-CoV-2 (COVID-19) by the numbers. eLife, 2020, 9: e57309. doi: 10.7554/eLife.57309
    [25]
    Narayanan K, Chen C J, Maeda J, et al. Nucleocapsid-independent specific viral RNA packaging via viral envelope protein and viral RNA signal. Journal of Virology, 2003, 77 (5): 2922–2927. doi: 10.1128/JVI.77.5.2922-2927.2003
    [26]
    Ahmed S F, Quadeer A A, McKay M R. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses, 2020, 12 (3): 254. doi: 10.3390/v12030254
    [27]
    Zhao H, Wu D, Nguyen A, et al. Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids. iScience, 2021, 24 (6): 102523. doi: 10.1016/j.isci.2021.102523
    [28]
    Tilocca B, Soggiu A, Sanguinetti M, et al. Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses. Microbes and Infection, 2020, 22: 188–194. doi: 10.1016/j.micinf.2020.04.002
    [29]
    Cubuk J, Alston J J, Incicco J J, et al. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nature Communications, 2021, 12 (1): 1936. doi: 10.1038/s41467-021-21953-3
    [30]
    Hurst K R, Koetzner C A, Masters P S. Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. Journal of Virology, 2009, 83 (14): 7221–7234. doi: 10.1128/JVI.00440-09
    [31]
    Fang H J, Chen Y Z, Li M S, et al. Thermostability of the N-terminal RNA-binding domain of the SARS-CoV nucleocapsid protein: Experiments and numerical simulations. Biophysical Journal, 2009, 96 (5): 1892–1901. doi: 10.1016/j.bpj.2008.10.045
    [32]
    Yang M, He S H, Chen X X, et al. Structural insight into the SARS-CoV-2 nucleocapsid protein C-terminal domain reveals a novel recognition mechanism for viral transcriptional regulatory sequences. Frontiers in Chemistry, 2021, 8: 624765. doi: 10.3389/fchem.2020.624765
    [33]
    Saikatendu K S, Joseph J S, Subramanian V, et al. Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein. Journal of Virology, 2007, 81 (8): 3913–3921. doi: 10.1128/JVI.02236-06
    [34]
    Chen C Y, Chang C K, Chang Y W, et al. Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA. Journal of Molecular Biology, 2007, 368 (4): 1075–1086. doi: 10.1016/j.jmb.2007.02.069
    [35]
    Chang C K, Chen C M, Chiang M H, et al. Transient oligomerization of the SARS-CoV N protein–implication for virus ribonucleoprotein packaging. PloS One, 2013, 8 (5): e65045. doi: 10.1371/journal.pone.0065045
    [36]
    Jia Z H, Liu C, Chen Y W, et al. Crystal structures of the SARS-CoV-2 nucleocapsid protein C-terminal domain and development of nucleocapsid-targeting nanobodies. The FEBS Journal, 2021. https://doi.org/10.1111/febs.16239.
    [37]
    de Wit E, van Doremalen N, Falzarano D, et al. SARS and MERS: recent insights into emerging coronaviruses. Nature Reviews Microbiology, 2016, 14 (8): 523–534. doi: 10.1038/nrmicro.2016.81
    [38]
    Zhou P, Yang X L, Wang X G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579 (7798): 270–273. doi: 10.1038/s41586-020-2012-7
    [39]
    Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Research, 2014, 42 (W1): W320–W324. doi: 10.1093/nar/gku316
    [40]
    Sievers F, Wilm A, Dineen D, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular Systems Biology, 2011, 7 (1): 539. doi: 10.1038/msb.2011.75
    [41]
    Gao T Y, Gao Y D, Liu X X, et al. Identification and functional analysis of the SARS-COV-2 nucleocapsid protein. BMC Microbiology, 2021, 21 (1): 58. doi: 10.1186/s12866-021-02107-3
    [42]
    Zeng W H, Liu G F, Ma H, et al. Biochemical characterization of SARS-CoV-2 nucleocapsid protein. Biochemical and Biophysical Research Communications, 2020, 527 (3): 618–623. doi: 10.1016/j.bbrc.2020.04.136
    [43]
    Hiscox J A, Wurm T, Wilson L, et al. The coronavirus infectious bronchitis virus nucleoprotein localizes to the nucleolus. Journal of Virology, 2001, 75 (1): 506–512. doi: 10.1128/JVI.75.1.506-512.2001
    [44]
    Peng Y, Du N, Lei Y Q, et al. Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design. The EMBO Journal, 2020, 39 (20): e105938. doi: 10.15252/embj.2020105938
    [45]
    Prasad K, Ahamad S, Kanipakam H, et al. Simultaneous inhibition of SARS-CoV-2 entry pathways by cyclosporine. ACS Chemical Neuroscience, 2021, 12 (5): 930–944. doi: 10.1021/acschemneuro.1c00019
    [46]
    Caruso Í P, Sanches K, Da Poian A T, et al. Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism. BioRxiv, 2020. https://doi.org/10.1101/2020.08.24.264465.
    [47]
    Kang S S, Yang M, Hong Z S, et al. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites. Acta Pharmaceutica Sinica B, 2020, 10 (7): 1228–1238. doi: 10.1016/j.apsb.2020.04.009
    [48]
    Fehr A R, Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods in Molecular Biology (Clifton, N. J. ), 2015, 1282: 1–23. doi: 10.1007/978-1-4939-2438-7_1
    [49]
    Cui L, Wang H Y, Ji Y X, et al. The nucleocapsid protein of coronaviruses acts as a viral suppressor of RNA silencing in mammalian cells. Journal of Virology, 2015, 89 (17): 9029–9043. doi: 10.1128/JVI.01331-15
    [50]
    Chang C K, Hsu Y L, Chang Y H, et al. Multiple nucleic acid binding sites and intrinsic disorder of severe acute respiratory syndrome coronavirus nucleocapsid protein: Implications for ribonucleocapsid protein packaging. Journal of Virology, 2009, 83 (5): 2255–2264. doi: 10.1128/JVI.02001-08
    [51]
    de Haan C A, Rottier P J. Molecular interactions in the assembly of coronaviruses. Advances in Virus Research, 2005, 64: 165–230. doi: 10.1016/S0065-3527(05)64006-7
    [52]
    Robbins S G, Frana M F, McGowan J J, et al. RNA-binding proteins of coronavirus MHV: detection of monomeric and multimeric N protein with an RNA overlay-protein blot assay. Virology, 1986, 150 (2): 402–410. doi: 10.1016/0042-6822(86)90305-3
    [53]
    Baric R S, Nelson G W, Fleming J O, et al. Interactions between coronavirus nucleocapsid protein and viral RNAs: implications for viral transcription. Journal of Virology, 1988, 62 (11): 4280–4287. doi: 10.1128/jvi.62.11.4280-4287.1988
    [54]
    Cong Y, Ulasli M, Schepers H, et al. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle. Journal of Virology, 2020, 94 (4): e01925–19. doi: 10.1128/JVI.01925-19
    [55]
    Fan H, Ooi A, Tan Y W, et al. The nucleocapsid protein of coronavirus infectious bronchitis virus: crystal structure of its N-terminal domain and multimerization properties. Structure, 2005, 13 (12): 1859–1868. doi: 10.1016/j.str.2005.08.021
    [56]
    Surjit M, Liu B, Kumar P, et al. The nucleocapsid protein of the SARS coronavirus is capable of self-association through a C-terminal 209 amino acid interaction domain. Biochemical and Biophysical Research Communications, 2004, 317 (4): 1030–1036. doi: 10.1016/j.bbrc.2004.03.154
    [57]
    Risco C, Antón I M, Enjuanes L, et al. The transmissible gastroenteritis coronavirus contains a spherical core shell consisting of M and N proteins. Journal of Virology, 1996, 70 (7): 4773–4777. doi: 10.1128/jvi.70.7.4773-4777.1996
    [58]
    Kuo L, Masters P S. Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. Journal of Virology, 2002, 76 (10): 4987–4999. doi: 10.1128/JVI.76.10.4987-4999.2002
    [59]
    Malone B, Urakova N, Snijder E J, et al. Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design. Nature Reviews Molecular Cell Biology, 2022, 23 (1): 21–39. doi: 10.1038/s41580-021-00432-z
    [60]
    Lo Y S, Lin S Y, Wang S M, et al. Oligomerization of the carboxyl terminal domain of the human coronavirus 229E nucleocapsid protein. FEBS Letters, 2013, 587 (2): 120–127. doi: 10.1016/j.febslet.2012.11.016
    [61]
    Grossoehme N E, Li L, Keane S C, et al. Coronavirus N protein N-terminal domain (NTD) specifically binds the transcriptional regulatory sequence (TRS) and melts TRS-cTRS RNA duplexes. Journal of Molecular Biology, 2009, 394 (3): 544–557. doi: 10.1016/j.jmb.2009.09.040
    [62]
    Gui M, Liu X, Guo D Y, et al. Electron microscopy studies of the coronavirus ribonucleoprotein complex. Protein & Cell, 2017, 8 (3): 219–224. doi: 10.1007/s13238-016-0352-8
    [63]
    Cong Y, Kriegenburg F, de Haan C A M, et al. Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers. Scientific Reports, 2017, 7 (1): 5740. doi: 10.1038/s41598-017-06062-w
    [64]
    Ma Y L, Tong X H, Xu X L, et al. Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus. Protein & Cell, 2010, 1 (7): 688–697. doi: 10.1007/s13238-010-0079-x
    [65]
    Kuo L, Hurst-Hess K R, Koetzner C A, et al. Analyses of coronavirus assembly interactions with interspecies membrane and nucleocapsid protein chimeras. Journal of Virology, 2016, 90 (9): 4357–4368. doi: 10.1128/JVI.03212-15
    [66]
    Shibabaw T, Molla M D, Teferi B, et al. Role of IFN and complements system: Innate immunity in SARS-CoV-2. Journal of Inflammation Research, 2020, 13: 507–518. doi: 10.2147/JIR.S267280
    [67]
    Amor S, Fernández Blanco L, Baker D. Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage. Clinical & Experimental Immunology, 2020, 202 (2): 193–209. doi: 10.1111/cei.13523
    [68]
    Ding S W, Han Q, Wang J, et al. Antiviral RNA interference in mammals. Current Opinion in Immunology, 2018, 54: 109–114. doi: 10.1016/j.coi.2018.06.010
    [69]
    Mu J, Xu J, Zhang L, et al. SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells. Science China Life Sciences, 2020, 63 (9): 1413–1416. doi: 10.1007/s11427-020-1692-1
    [70]
    Catanzaro M, Fagiani F, Racchi M, et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduction and Targeted Therapy, 2020, 5 (1): 84. doi: 10.1038/s41392-020-0191-1
    [71]
    Li J Y, Liao C H, Wang Q, et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Research, 2020, 286: 198074. doi: 10.1016/j.virusres.2020.198074
    [72]
    Zheng Y, Zhuang M W, Han L L, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling. Signal Transduction and Targeted Therapy, 2020, 5 (1): 299. doi: 10.1038/s41392-020-00438-7
    [73]
    Chen K L, Xiao F, Hu D W, et al. SARS-CoV-2 nucleocapsid protein interacts with RIG-I and represses RIG-mediated IFN-β production. Viruses, 2020, 13 (1): 47. doi: 10.3390/v13010047
    [74]
    Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 2020, 369 (6504): 718–724. doi: 10.1126/science.abc6027
    [75]
    Tian W M, Zhang N, Jin R H, et al. Immune suppression in the early stage of COVID-19 disease. Nature Communications, 2020, 11 (1): 5859. doi: 10.1038/s41467-020-19706-9
    [76]
    Zhao Y H, Sui L Y, Wu P, et al. A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response. Signal Transduction and Targeted Therapy, 2021, 6 (1): 331. doi: 10.1038/s41392-021-00742-w
    [77]
    Novoa R R, Calderita G, Arranz R, et al. Virus factories: associations of cell organelles for viral replication and morphogenesis. Biology of the Cell, 2005, 97 (2): 147–172. doi: 10.1042/BC20040058
    [78]
    Savastano A, Ibáñez de Opakua A, Rankovic M, et al. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nature Communications, 2020, 11 (1): 6041. doi: 10.1038/s41467-020-19843-1
    [79]
    Iserman C, Roden C A, Boerneke M A, et al. Genomic RNA elements drive phase separation of the SARS-CoV-2 nucleocapsid. Molecular Cell, 2020, 80 (6): 1078–1091.e6. doi: 10.1016/j.molcel.2020.11.041
    [80]
    Carlson C R, Asfaha J B, Ghent C M, et al. Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions. Molecular Cell, 2020, 80 (6): 1092–1103.e4. doi: 10.1016/j.molcel.2020.11.025
    [81]
    Chen H, Cui Y, Han X L, et al. Liquid–liquid phase separation by SARS-CoV-2 nucleocapsid protein and RNA. Cell Research, 2020, 30 (12): 1143–1145. doi: 10.1038/s41422-020-00408-2
    [82]
    Asselah T, Durantel D, Pasmant E, et al. COVID-19: Discovery, diagnostics and drug development. Journal of Hepatology, 2021, 74 (1): 168–184. doi: 10.1016/j.jhep.2020.09.031
    [83]
    Woloshin S, Patel N, Kesselheim A S. False negative tests for SARS-CoV-2 infection—challenges and implications. The New England Journal of Medicine, 2020, 383 (6): e38. doi: 10.1056/NEJMp2015897
    [84]
    Hartley G E, Edwards E S J, Aui P M, et al. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence. Science Immunology, 2020, 5 (54): eabf8891. doi: 10.1126/sciimmunol.abf8891
    [85]
    Li J, Lillehoj P B. Microfluidic magneto immunosensor for rapid, high sensitivity measurements of SARS-CoV-2 Nucleocapsid protein in serum. ACS Sensors, 2021, 6 (3): 1270–1278. doi: 10.1021/acssensors.0c02561
    [86]
    Amrun S N, Lee C Y, Lee B, et al. Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity. EBioMedicine, 2020, 58: 102911. doi: 10.1016/j.ebiom.2020.102911
    [87]
    Hachim A, Kavian N, Cohen C A, et al. Beyond the Spike: identification of viral targets of the antibody response to SARS-CoV-2 in COVID-19 patients. medRxiv, 2020. https://doi.org/10.1101/2020.04.30.20085670.
    [88]
    Zhang W, Du R H, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections, 2020, 9 (1): 386–389. doi: 10.1080/22221751.2020.1729071
    [89]
    Guo L, Ren L L, Yang S Y, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clinical Infectious Diseases, 2020, 71 (15): 778–785. doi: 10.1093/cid/ciaa310
    [90]
    Tomaras G D, Haynes B F. HIV-1-specific antibody responses during acute and chronic HIV-1 infection. Current Opinion in HIV and AIDS, 2009, 4 (5): 373–379. doi: 10.1097/COH.0b013e32832f00c0
    [91]
    Li T, Wang L, Wang H H, et al. Serum SARS-COV-2 nucleocapsid protein: A sensitivity and specificity early diagnostic marker for SARS-COV-2 infection. Frontiers in Cellular and Infection Microbiology, 2020, 10: 470. doi: 10.3389/fcimb.2020.00470
    [92]
    Lyu A H, Jin T C, Wang S S, et al. Automatic label-free immunoassay with high sensitivity for rapid detection of SARS-CoV-2 nucleocapsid protein based on chemiluminescent magnetic beads. Sensors and Actuators B:Chemical, 2021, 349: 130739. doi: 10.1016/j.snb.2021.130739
    [93]
    Wang S S, Shu J N, Lyu A H, et al. Label-free immunoassay for sensitive and rapid detection of the SARS-CoV-2 antigen based on functionalized magnetic nanobeads with chemiluminescence and immunoactivity. Analytical Chemistry, 2021, 93 (42): 14238–14246. doi: 10.1021/acs.analchem.1c03208
    [94]
    Wang Y T, Long X Y, Ding X, et al. Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2. European Journal of Medicinal Chemistry, 2022, 227: 113966. doi: 10.1016/j.ejmech.2021.113966
    [95]
    Lin S M, Lin S C, Hsu J N, et al. Structure-based stabilization of non-native protein–protein interactions of coronavirus nucleocapsid proteins in antiviral drug design. Journal of Medicinal Chemistry, 2020, 63 (6): 3131–3141. doi: 10.1021/acs.jmedchem.9b01913
    [96]
    Zhao M, Yu Y, Sun L M, et al. GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein. Nature Communications, 2021, 12 (1): 2114. doi: 10.1038/s41467-021-22297-8
    [97]
    Chen R E, Zhang X, Case J B, et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nature Medicine, 2021, 27 (4): 717–726. doi: 10.1038/s41591-021-01294-w
    [98]
    McBride R, van Zyl M, Fielding B C. The coronavirus nucleocapsid is a multifunctional protein. Viruses, 2014, 6 (8): 2991–3018. doi: 10.3390/v6082991
    [99]
    Sun B Q, Feng Y, Mo X N, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerging Microbes & Infections, 2020, 9 (1): 940–948. doi: 10.1080/22221751.2020.1762515
    [100]
    Qu J X, Wu C, Li X Y, et al. Profile of immunoglobulin G and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases, 2020, 71 (16): 2255–2258. doi: 10.1093/cid/ciaa489
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