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Abstract

The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as ‘long COVID’). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a ‘cytokine storm’ and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus’s ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-11-10
2024-07-22
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References

  1. Almas T, Malik J, Alsubai AK, Jawad Zaidi SM, Iqbal R et al. Post-acute COVID-19 syndrome and its prolonged effects: an updated systematic review. Ann Med Surg 2022; 80:103995 [View Article]
    [Google Scholar]
  2. Du M, Ma Y, Deng J, Liu M, Liu J. Comparison of long COVID-19 caused by different SARS-CoV-2 strains: a systematic review and meta-analysis. Int J Environ Res Public Health 2022; 19:16010 [View Article] [PubMed]
    [Google Scholar]
  3. Montani D, Savale L, Noel N, Meyrignac O, Colle R et al. Post-acute COVID-19 syndrome. Eur Respir Rev 2022; 31:210185 [View Article] [PubMed]
    [Google Scholar]
  4. O’Mahoney LL, Routen A, Gillies C, Ekezie W, Welford A et al. The prevalence and long-term health effects of long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis. EClinicalMedicine 2023; 55:101762 [View Article] [PubMed]
    [Google Scholar]
  5. O’Mahoney L, Khunti K. Long covid: risk factors, outcomes, and future directions for research. BMJ Med 2022; 1:e000257 [View Article] [PubMed]
    [Google Scholar]
  6. Deer RR, Rock MA, Vasilevsky N, Carmody L, Rando H et al. Characterizing long COVID: deep phenotype of a complex condition. EBioMedicine 2021; 74:103722 [View Article] [PubMed]
    [Google Scholar]
  7. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol 2023; 21:133–146 [View Article]
    [Google Scholar]
  8. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579:270–273 [View Article]
    [Google Scholar]
  9. Zhu N, Zhang D, Wang W, Li X, Yang B et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382:727–733 [View Article] [PubMed]
    [Google Scholar]
  10. Lu R, Zhao X, Li J, Niu P, Yang B et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565–574 [View Article] [PubMed]
    [Google Scholar]
  11. Kim J-M, Chung Y-S, Jo HJ, Lee N-J, Kim MS et al. Identification of coronavirus isolated from a patient in Korea with COVID-19. Osong Public Health Res Perspect 2020; 11:3–7 [View Article] [PubMed]
    [Google Scholar]
  12. V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 2021; 19:155–170 [View Article] [PubMed]
    [Google Scholar]
  13. Hartenian E, Nandakumar D, Lari A, Ly M, Tucker JM et al. The molecular virology of coronaviruses. J Biol Chem 2020; 295:12910–12934 [View Article] [PubMed]
    [Google Scholar]
  14. Jahirul Islam M, Nawal Islam N, Siddik Alom M, Kabir M, Halim MA. A review on structural, non-structural, and accessory proteins of SARS-CoV-2: highlighting drug target sites. Immunobiology 2023; 228:152302 [View Article] [PubMed]
    [Google Scholar]
  15. Kaur N, Singh R, Dar Z, Bijarnia RK, Dhingra N et al. Genetic comparison among various coronavirus strains for the identification of potential vaccine targets of SARS-CoV2. Infect Genet Evol 2021; 89:104490 [View Article] [PubMed]
    [Google Scholar]
  16. Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol 2021; 19:685–700 [View Article] [PubMed]
    [Google Scholar]
  17. Wu F, Zhao S, Yu B, Chen Y-M, Wang W et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 580:E7 [View Article] [PubMed]
    [Google Scholar]
  18. Fan K, Wei P, Feng Q, Chen S, Huang C et al. Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase. J Biol Chem 2004; 279:1637–1642 [View Article] [PubMed]
    [Google Scholar]
  19. Harcourt BH, Jukneliene D, Kanjanahaluethai A, Bechill J, Severson KM et al. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. J Virol 2004; 78:13600–13612 [View Article] [PubMed]
    [Google Scholar]
  20. Jin Z, Du X, Xu Y, Deng Y, Liu M et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020; 582:289–293 [View Article]
    [Google Scholar]
  21. Klemm T, Ebert G, Calleja DJ, Allison CC, Richardson LW et al. Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2. EMBO J 2020; 39:e106275 [View Article] [PubMed]
    [Google Scholar]
  22. Blackford AN, Jackson SP. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol Cell 2017; 66:801–817 [View Article] [PubMed]
    [Google Scholar]
  23. Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010; 40:179–204 [View Article] [PubMed]
    [Google Scholar]
  24. Davis AJ, Chen DJ. DNA double strand break repair via non-homologous end-joining. Transl Cancer Res 2013; 2:130–143 [View Article] [PubMed]
    [Google Scholar]
  25. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 2017; 18:495–506 [View Article] [PubMed]
    [Google Scholar]
  26. Spies J, Polasek-Sedlackova H, Lukas J, Somyajit K. Homologous recombination as a fundamental genome surveillance mechanism during DNA replication. Genes 2021; 12:12 [View Article] [PubMed]
    [Google Scholar]
  27. Wright WD, Shah SS, Heyer WD. Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem 2018; 293:10524–10535 [View Article] [PubMed]
    [Google Scholar]
  28. Krejci L, Altmannova V, Spirek M, Zhao X. Homologous recombination and its regulation. Nucleic Acids Res 2012; 40:5795–5818 [View Article] [PubMed]
    [Google Scholar]
  29. Li Z, Pearlman AH, Hsieh P. DNA mismatch repair and the DNA damage response. DNA Repair 2016; 38:94–101 [View Article] [PubMed]
    [Google Scholar]
  30. Li G-M. Mechanisms and functions of DNA mismatch repair. Cell Res 2008; 18:85–98 [View Article]
    [Google Scholar]
  31. Ijsselsteijn R, Jansen JG, de Wind N. DNA mismatch repair-dependent DNA damage responses and cancer. DNA Repair 2020; 93:102923 [View Article] [PubMed]
    [Google Scholar]
  32. Fishel R. Mismatch repair. J Biol Chem 2015; 290:26395–26403 [View Article] [PubMed]
    [Google Scholar]
  33. Hegde ML, Hazra TK, Mitra S. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 2008; 18:27–47 [View Article] [PubMed]
    [Google Scholar]
  34. Dianov GL, Hübscher U. Mammalian base excision repair: the forgotten archangel. Nucleic Acids Res 2013; 41:3483–3490 [View Article]
    [Google Scholar]
  35. Spivak G. Nucleotide excision repair in humans. DNA Repair 2015; 36:13–18 [View Article] [PubMed]
    [Google Scholar]
  36. Reardon JT, Sancar A. Nucleotide excision repair. Prog Nucleic Acid Res Mol Biol 2005; 79:183–235 [View Article] [PubMed]
    [Google Scholar]
  37. Ceccaldi R, Sarangi P, D’Andrea AD. The Fanconi anaemia pathway: new players and new functions. Nat Rev Mol Cell Biol 2016; 17:337–349 [View Article] [PubMed]
    [Google Scholar]
  38. D’Andrea AD, Grompe M. The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 2003; 3:23–34 [View Article] [PubMed]
    [Google Scholar]
  39. Taylor AMR, Rothblum-Oviatt C, Ellis NA, Hickson ID, Meyer S et al. Chromosome instability syndromes. Nat Rev Dis Primers 2019; 5:64 [View Article] [PubMed]
    [Google Scholar]
  40. Kaina B, Christmann M, Naumann S, Roos WP. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair 2007; 6:1079–1099 [View Article] [PubMed]
    [Google Scholar]
  41. Gutierrez R, O’Connor TR. DNA direct reversal repair and alkylating agent drug resistance. Cancer Drug Resist 2021; 4:414–423 [View Article] [PubMed]
    [Google Scholar]
  42. Hollingworth R, Grand RJ. Modulation of DNA damage and repair pathways by human tumour viruses. Viruses 2015; 7:2542–2591 [View Article]
    [Google Scholar]
  43. Ryan EL, Hollingworth R, Grand RJ. Activation of the DNA damage response by RNA viruses. Biomolecules 2016; 6:2 [View Article] [PubMed]
    [Google Scholar]
  44. Turnell AS, Grand RJ. DNA viruses and the cellular DNA-damage response. J Gen Virol 2012; 93:2076–2097 [View Article] [PubMed]
    [Google Scholar]
  45. Pancholi NJ, Price AM, Weitzman MD. Take your PIKK: tumour viruses and DNA damage response pathways. Philos Trans R Soc Lond B Biol Sci 2017; 372:1732 [View Article] [PubMed]
    [Google Scholar]
  46. Weitzman MD, Fradet-Turcotte A. Virus DNA replication and the host DNA damage response. Annu Rev Virol 2018; 5:141–164 [View Article] [PubMed]
    [Google Scholar]
  47. Luftig MA. Viruses and the DNA damage response: activation and antagonism. Annu Rev Virol 2014; 1:605–625 [View Article] [PubMed]
    [Google Scholar]
  48. Weitzman MD, Lilley CE, Chaurushiya MS. Genomes in conflict: maintaining genome integrity during virus infection. Annu Rev Microbiol 2010; 64:61–81 [View Article] [PubMed]
    [Google Scholar]
  49. Stracker TH, Carson CT, Weitzman MD. Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature 2002; 418:348–352 [View Article] [PubMed]
    [Google Scholar]
  50. Orazio NI, Naeger CM, Karlseder J, Weitzman MD. The adenovirus E1b55K/E4orf6 complex induces degradation of the bloom helicase during infection. J Virol 2011; 85:1887–1892 [View Article] [PubMed]
    [Google Scholar]
  51. Chaurushiya MS, Lilley CE, Aslanian A, Meisenhelder J, Scott DC et al. Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain. Mol Cell 2012; 46:79–90 [View Article] [PubMed]
    [Google Scholar]
  52. Parkinson J, Lees-Miller SP, Everett RD. Herpes simplex virus type 1 immediate-early protein vmw110 induces the proteasome-dependent degradation of the catalytic subunit of DNA-dependent protein kinase. J Virol 1999; 73:650–657 [View Article] [PubMed]
    [Google Scholar]
  53. Xiaofei E, Kowalik TF. The DNA damage response induced by infection with human cytomegalovirus and other viruses. Viruses 2014; 6:2155–2185 [View Article] [PubMed]
    [Google Scholar]
  54. Hagemeier SR, Barlow EA, Meng Q, Kenney SC. The cellular ataxia telangiectasia-mutated kinase promotes epstein-barr virus lytic reactivation in response to multiple different types of lytic reactivation-inducing stimuli. J Virol 2012; 86:13360–13370 [View Article] [PubMed]
    [Google Scholar]
  55. Hollingworth R, Horniblow RD, Forrest C, Stewart GS, Grand RJ. Localization of double-strand break repair proteins to viral replication compartments following lytic reactivation of Kaposi’s sarcoma-associated herpesvirus. J Virol 2017; 91:e00930-17 [View Article] [PubMed]
    [Google Scholar]
  56. Lilley CE, Carson CT, Muotri AR, Gage FH, Weitzman MD. DNA repair proteins affect the lifecycle of herpes simplex virus 1. Proc Natl Acad Sci U S A 2005; 102:5844–5849 [View Article] [PubMed]
    [Google Scholar]
  57. Li R, Zhu J, Xie Z, Liao G, Liu J et al. Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication. Cell Host Microbe 2011; 10:390–400 [View Article] [PubMed]
    [Google Scholar]
  58. Shi Y, Dodson GE, Shaikh S, Rundell K, Tibbetts RS. Ataxia-telangiectasia-mutated (ATM) is a T-antigen kinase that controls SV40 viral replication in vivo. J Biol Chem 2005; 280:40195–40200 [View Article] [PubMed]
    [Google Scholar]
  59. Dahl J, You J, Benjamin TL. Induction and utilization of an ATM signaling pathway by polyomavirus. J Virol 2005; 79:13007–13017 [View Article] [PubMed]
    [Google Scholar]
  60. Hollingworth R, Skalka GL, Stewart GS, Hislop AD, Blackbourn DJ et al. Activation of DNA damage response pathways during lytic replication of KSHV. Viruses 2015; 7:2908–2927 [View Article] [PubMed]
    [Google Scholar]
  61. Blackford AN, Bruton RK, Dirlik O, Stewart GS, Taylor AMR et al. A role for E1B-AP5 in ATR signaling pathways during adenovirus infection. J Virol 2008; 82:7640–7652 [View Article] [PubMed]
    [Google Scholar]
  62. Daikoku T, Kudoh A, Sugaya Y, Iwahori S, Shirata N et al. Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments. J Biol Chem 2006; 281:11422–11430 [View Article] [PubMed]
    [Google Scholar]
  63. Gillespie KA, Mehta KP, Laimins LA, Moody CA. Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers. J Virol 2012; 86:9520–9526 [View Article] [PubMed]
    [Google Scholar]
  64. Hau PM, Deng W, Jia L, Yang J, Tsurumi T et al. Role of ATM in the formation of the replication compartment during lytic replication of Epstein-Barr virus in nasopharyngeal epithelial cells. J Virol 2015; 89:652–668 [View Article] [PubMed]
    [Google Scholar]
  65. Tsang SH, Wang X, Li J, Buck CB, You J. Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication. J Virol 2014; 88:3285–3297 [View Article] [PubMed]
    [Google Scholar]
  66. Denison MR. Seeking membranes: positive-strand RNA virus replication complexes. PLoS Biol 2008; 6:e270 [View Article] [PubMed]
    [Google Scholar]
  67. Zawilska JB, Lagodzinski A, Berezinska M. COVID-19: from the structure and replication cycle of SARS-CoV-2 to its disease symptoms and treatment. J Physiol Pharmacol 2021; 72: [View Article] [PubMed]
    [Google Scholar]
  68. Howley PM, Knipe DM, Whelan S, Freed EO, Cohen JL. Fields Virology: Volume 3, RNA Viruses. Wolters Kluwer Philadelphia; 2022
  69. Clavarino G, Cláudio N, Couderc T, Dalet A, Judith D et al. Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection. PLoS Pathog 2012; 8:e1002708 [View Article] [PubMed]
    [Google Scholar]
  70. Nargi-Aizenman JL, Simbulan-Rosenthal CM, Kelly TA, Smulson ME, Griffin DE. Rapid activation of poly(ADP-ribose) polymerase contributes to Sindbis virus and staurosporine-induced apoptotic cell death. Virology 2002; 293:164–171 [View Article] [PubMed]
    [Google Scholar]
  71. Tachiwana H, Shimura M, Nakai-Murakami C, Tokunaga K, Takizawa Y et al. HIV-1 Vpr induces DNA double-strand breaks. Cancer Res 2006; 66:627–631 [View Article] [PubMed]
    [Google Scholar]
  72. Nakai-Murakami C, Shimura M, Kinomoto M, Takizawa Y, Tokunaga K et al. HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination. Oncogene 2007; 26:477–486 [View Article] [PubMed]
    [Google Scholar]
  73. Li N, Parrish M, Chan TK, Yin L, Rai P et al. Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration. Cell Mol Life Sci 2015; 72:2973–2988 [View Article] [PubMed]
    [Google Scholar]
  74. Vijaya Lakshmi AN, Ramana MV, Vijayashree B, Ahuja YR, Sharma G. Detection of influenza virus induced DNA damage by comet assay. Mutat Res 1999; 442:53–58 [View Article] [PubMed]
    [Google Scholar]
  75. Pánico P, Ostrosky-Wegman P, Salazar AM. The potential role of COVID-19 in the induction of DNA damage. Mutat Res Rev Mutat Res 2022; 789:108411 [View Article] [PubMed]
    [Google Scholar]
  76. Papanikolaou C, Rapti V, Stellas D, Stefanou DT, Syrigos K et al. Delineating the SARS-CoV-2 induced interplay between the host immune system and the DNA damage response network. Vaccines 2022; 10:10 [View Article] [PubMed]
    [Google Scholar]
  77. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426:450–454 [View Article] [PubMed]
    [Google Scholar]
  78. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5:562–569 [View Article] [PubMed]
    [Google Scholar]
  79. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181:271–280 [View Article] [PubMed]
    [Google Scholar]
  80. Lan J, Ge J, Yu J, Shan S, Zhou H et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020; 581:215–220 [View Article]
    [Google Scholar]
  81. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020; 183:1735 [View Article] [PubMed]
    [Google Scholar]
  82. Hoffmann M, Kleine-Weber H, Pöhlmann S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell 2020; 78:779–784 [View Article] [PubMed]
    [Google Scholar]
  83. Sawicki SG, Sawicki DL. Coronavirus transcription: a perspective. Curr Top Microbiol Immunol 2005; 287:31–55 [View Article] [PubMed]
    [Google Scholar]
  84. Kim D, Lee J-Y, Yang J-S, Kim JW, Kim VN et al. The architecture of SARS-CoV-2 transcriptome. Cell 2020; 181:914–921 [View Article]
    [Google Scholar]
  85. Sola I, Almazán F, Zúñiga S, Enjuanes L. Continuous and discontinuous RNA synthesis in coronaviruses. Annu Rev Virol 2015; 2:265–288 [View Article] [PubMed]
    [Google Scholar]
  86. Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D et al. The coding capacity of SARS-CoV-2. Nature 2021; 589:125–130 [View Article]
    [Google Scholar]
  87. Lei J, Kusov Y, Hilgenfeld R. Nsp3 of coronaviruses: structures and functions of a large multi-domain protein. Antiviral Res 2018; 149:58–74 [View Article] [PubMed]
    [Google Scholar]
  88. Zhang L, Lin D, Sun X, Curth U, Drosten C et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science 2020; 368:409–412 [View Article]
    [Google Scholar]
  89. Scott BM, Lacasse V, Blom DG, Tonner PD, Blom NS. Predicted coronavirus Nsp5 protease cleavage sites in the human proteome. BMC Genom Data 2022; 23:25 [View Article] [PubMed]
    [Google Scholar]
  90. Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science 2020; 369:1249–1255 [View Article] [PubMed]
    [Google Scholar]
  91. Schubert K, Karousis ED, Jomaa A, Scaiola A, Echeverria B et al. SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Nat Struct Mol Biol 2020; 27:1094 [View Article] [PubMed]
    [Google Scholar]
  92. Kamitani W, Huang C, Narayanan K, Lokugamage KG, Makino S. A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. Nat Struct Mol Biol 2009; 16:1134–1140 [View Article] [PubMed]
    [Google Scholar]
  93. Kakavandi S, Zare I, VaezJalali M, Dadashi M, Azarian M et al. Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases. Cell Commun Signal 2023; 21:110 [View Article] [PubMed]
    [Google Scholar]
  94. Arya R, Kumari S, Pandey B, Mistry H, Bihani SC et al. Structural insights into SARS-CoV-2 proteins. J Mol Biol 2021; 433:166725 [View Article] [PubMed]
    [Google Scholar]
  95. Gao Y, Yan L, Huang Y, Liu F, Zhao Y et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 2020; 368:779–782 [View Article] [PubMed]
    [Google Scholar]
  96. Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun 2019; 10:2342 [View Article] [PubMed]
    [Google Scholar]
  97. Konkolova E, Klima M, Nencka R, Boura E. Structural analysis of the putative SARS-CoV-2 primase complex. J Struct Biol 2020; 211:107548 [View Article] [PubMed]
    [Google Scholar]
  98. Ma Y, Wu L, Shaw N, Gao Y, Wang J et al. Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex. Proc Natl Acad Sci U S A 2015; 112:9436–9441 [View Article] [PubMed]
    [Google Scholar]
  99. Baddock HT, Brolih S, Yosaatmadja Y, Ratnaweera M, Bielinski M et al. Characterization of the SARS-CoV-2 ExoN (nsp14ExoN-nsp10) complex: implications for its role in viral genome stability and inhibitor identification. Nucleic Acids Res 2022; 50:1484–1500 [View Article] [PubMed]
    [Google Scholar]
  100. Ogando NS, Zevenhoven-Dobbe JC, van der Meer Y, Bredenbeek PJ, Posthuma CC et al. The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2. J Virol 2020; 94:e01246-20 [View Article] [PubMed]
    [Google Scholar]
  101. Chen J, Malone B, Llewellyn E, Grasso M, Shelton PMM et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex. Cell 2020; 182:1560–1573 [View Article]
    [Google Scholar]
  102. Newman JA, Douangamath A, Yadzani S, Yosaatmadja Y, Aimon A et al. Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase. Nat Commun 2021; 12:4848 [View Article] [PubMed]
    [Google Scholar]
  103. Huang T, Snell KC, Kalia N, Gardezi S, Guo L et al. Kinetic analysis of RNA cleavage by coronavirus Nsp15 endonuclease: evidence for acid-base catalysis and substrate-dependent metal ion activation. J Biol Chem 2023; 299:104787 [View Article] [PubMed]
    [Google Scholar]
  104. Frazier MN, Dillard LB, Krahn JM, Perera L, Williams JG et al. Characterization of SARS2 Nsp15 nuclease activity reveals it’s mad about U. Nucleic Acids Res 2021; 49:10136–10149 [View Article] [PubMed]
    [Google Scholar]
  105. Nencka R, Silhan J, Klima M, Otava T, Kocek H et al. Coronaviral RNA-methyltransferases: function, structure and inhibition. Nucleic Acids Res 2022; 50:635–650 [View Article] [PubMed]
    [Google Scholar]
  106. Krafcikova P, Silhan J, Nencka R, Boura E. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. Nat Commun 2020; 11:3717 [View Article] [PubMed]
    [Google Scholar]
  107. Lu S, Ye Q, Singh D, Cao Y, Diedrich JK et al. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat Commun 2021; 12: [View Article]
    [Google Scholar]
  108. Zheng Y, Zhuang M-W, Han L, Zhang J, Nan M-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 Transduct Target Ther 2020; 5:299 [View Article] [PubMed]
    [Google Scholar]
  109. Lei X, Dong X, Ma R, Wang W, Xiao X et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat Commun 2020; 11:3810 [View Article] [PubMed]
    [Google Scholar]
  110. Zhang Z, Nomura N, Muramoto Y, Ekimoto T, Uemura T et al. Structure of SARS-CoV-2 membrane protein essential for virus assembly. Nat Commun 2022; 13: [View Article]
    [Google Scholar]
  111. Marques-Pereira C, Pires MN, Gouveia RP, Pereira NN, Caniceiro AB et al. SARS-CoV-2 membrane protein: from genomic data to structural new insights. Int J Mol Sci 2022; 23:2986 [View Article] [PubMed]
    [Google Scholar]
  112. Bai Z, Cao Y, Liu W, Li J. 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; 13:1115 [View Article] [PubMed]
    [Google Scholar]
  113. Savastano A, Ibáñez de Opakua A, Rankovic M, Zweckstetter M. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nat Commun 2020; 11:6041 [View Article] [PubMed]
    [Google Scholar]
  114. Gao T, Gao Y, Liu X, Nie Z, Sun H et al. Identification and functional analysis of the SARS-COV-2 nucleocapsid protein. BMC Microbiol 2021; 21:58 [View Article] [PubMed]
    [Google Scholar]
  115. Wu W, Cheng Y, Zhou H, Sun C, Zhang S. The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics. Virol J 2023; 20:6 [View Article] [PubMed]
    [Google Scholar]
  116. Perdikari TM, Murthy AC, Ryan VH, Watters S, Naik MT et al. SARS‐CoV‐2 nucleocapsid protein phase‐separates with RNA and with human hnRNPs. The EMBO Journal 2020; 39:24 [View Article]
    [Google Scholar]
  117. Zhu C, He G, Yin Q, Zeng L, Ye X et al. Molecular biology of the SARs-CoV-2 spike protein: a review of current knowledge. J Med Virol 2021; 93:5729–5741 [View Article] [PubMed]
    [Google Scholar]
  118. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367:1260–1263 [View Article]
    [Google Scholar]
  119. Yan R, Zhang Y, Li Y, Xia L, Guo Y et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020; 367:1444–1448 [View Article]
    [Google Scholar]
  120. Cao Y, Yang R, Lee I, Zhang W, Sun J et al. Characterization of the SARS-CoV-2 E protein: sequence, structure, viroporin, and inhibitors. Protein Sci 2021; 30:1114–1130 [View Article] [PubMed]
    [Google Scholar]
  121. Zhou S, Lv P, Li M, Chen Z, Xin H et al. SARS-CoV-2 E protein: pathogenesis and potential therapeutic development. Biomed Pharmacother 2023; 159:114242 [View Article] [PubMed]
    [Google Scholar]
  122. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. SARS-CoV-2 accessory proteins in viral pathogenesis: knowns and unknowns. Front Immunol 2021; 12:708264 [View Article]
    [Google Scholar]
  123. Hurtado-Tamayo J, Requena-Platek R, Enjuanes L, Bello-Perez M, Sola I. Contribution to pathogenesis of accessory proteins of deadly human coronaviruses. Front Cell Infect Microbiol 2023; 13:1166839 [View Article] [PubMed]
    [Google Scholar]
  124. Shang J, Han N, Chen Z, Peng Y, Li L et al. Compositional diversity and evolutionary pattern of coronavirus accessory proteins. Brief Bioinform 2021; 22:1267–1278 [View Article] [PubMed]
    [Google Scholar]
  125. Xia H, Cao Z, Xie X, Zhang X, Chen JY-C et al. Evasion of type I interferon by SARS-CoV-2. Cell Rep 2020; 33:108234 [View Article] [PubMed]
    [Google Scholar]
  126. Rashid F, Xie Z, Suleman M, Shah A, Khan S et al. Roles and functions of SARS-CoV-2 proteins in host immune evasion. Front Immunol 2022; 13:940756 [View Article] [PubMed]
    [Google Scholar]
  127. Zandi M, Shafaati M, Kalantar-Neyestanaki D, Pourghadamyari H, Fani M et al. The role of SARS-CoV-2 accessory proteins in immune evasion. Biomed Pharmacother 2022; 156:113889 [View Article] [PubMed]
    [Google Scholar]
  128. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature 2000; 408:433–439 [View Article] [PubMed]
    [Google Scholar]
  129. Lukas J, Lukas C, Bartek J. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair 2004; 3:997–1007 [View Article] [PubMed]
    [Google Scholar]
  130. Nascimento R, Costa H, Parkhouse RME. Virus manipulation of cell cycle. Protoplasma 2012; 249:519–528 [View Article] [PubMed]
    [Google Scholar]
  131. Berk AJ. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Oncogene 2005; 24:7673–7685 [View Article] [PubMed]
    [Google Scholar]
  132. Ben-Israel H, Kleinberger T. Adenovirus and cell cycle control. Front Biosci 2002; 7:d1369–95 [View Article] [PubMed]
    [Google Scholar]
  133. Chiu Y-F, Sugden AU, Sugden B. Epstein-Barr viral productive amplification reprograms nuclear architecture, DNA replication, and histone deposition. Cell Host Microbe 2013; 14:607–618 [View Article] [PubMed]
    [Google Scholar]
  134. Hollingworth R, Stewart GS, Grand RJ. Productive herpesvirus lytic replication in primary effusion lymphoma cells requires S-phase entry. J Gen Virol 2020; 101:873–883 [View Article] [PubMed]
    [Google Scholar]
  135. Baer A, Austin D, Narayanan A, Popova T, Kainulainen M et al. Induction of DNA damage signaling upon Rift Valley fever virus infection results in cell cycle arrest and increased viral replication. J Biol Chem 2012; 287:7399–7410 [View Article] [PubMed]
    [Google Scholar]
  136. Gioia U, Tavella S, Martínez-Orellana P, Cicio G, Colliva A et al. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nat Cell Biol 2023; 25:550–564 [View Article] [PubMed]
    [Google Scholar]
  137. Quan L, Sun X, Xu L, Chen RA, Liu DX. Coronavirus RNA-dependent RNA polymerase interacts with the p50 regulatory subunit of host DNA polymerase delta and plays a synergistic role with RNA helicase in the induction of DNA damage response and cell cycle arrest in the S phase. Emerg Microbes Infect 2023; 12:e2176008 [View Article] [PubMed]
    [Google Scholar]
  138. Xu LH, Huang M, Fang SG, Liu DX. Coronavirus infection induces DNA replication stress partly through interaction of its nonstructural protein 13 with the p125 subunit of DNA polymerase δ. J Biol Chem 2011; 286:39546–39559 [View Article] [PubMed]
    [Google Scholar]
  139. Wang W, Chen J, Hu D, Pan P, Liang L et al. SARS-CoV-2 N protein induces acute kidney injury via Smad3-dependent G1 cell cycle arrest mechanism. Adv Sci 2022; 9:e2103248 [View Article] [PubMed]
    [Google Scholar]
  140. Wu W, Wang W, Liang L, Chen J, Wei B et al. Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest. Mol Ther 2023; 31:344–361 [View Article] [PubMed]
    [Google Scholar]
  141. Gao T, Gao Y, Liu X, Nie Z, Sun H et al. Identification and functional analysis of the SARS-COV-2 nucleocapsid protein. BMC Microbiol 2021; 21:58 [View Article] [PubMed]
    [Google Scholar]
  142. Surjit M, Liu B, Chow VTK, Lal SK. The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells. J Biol Chem 2006; 281:10669–10681 [View Article] [PubMed]
    [Google Scholar]
  143. Su M, Chen Y, Qi S, Shi D, Feng L et al. A mini-review on cell cycle regulation of coronavirus infection. Front Vet Sci 2020; 7:586826 [View Article]
    [Google Scholar]
  144. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 2020; 182:685–712 [View Article]
    [Google Scholar]
  145. Lee J, Hong F, Kwon S, Kim SS, Kim DO et al. Activation of p38 MAPK induces cell cycle arrest via inhibition of Raf/ERK pathway during muscle differentiation. Biochem Biophys Res Commun 2002; 298:765–771 [View Article] [PubMed]
    [Google Scholar]
  146. Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 1992; 257:1955–1957 [View Article] [PubMed]
    [Google Scholar]
  147. Mueller PR, Coleman TR, Kumagai A, Dunphy WG. Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 1995; 270:86–90 [View Article] [PubMed]
    [Google Scholar]
  148. Välikangas T, Junttila S, Rytkönen KT, Kukkonen-Macchi A, Suomi T et al. COVID-19-specific transcriptomic signature detectable in blood across multiple cohorts. Front Genet 2022; 13:929887 [View Article] [PubMed]
    [Google Scholar]
  149. Bittar C, Shrivastava S, Bhanja Chowdhury J, Rahal P, Ray RB. Hepatitis C virus NS2 protein inhibits DNA damage pathway by sequestering p53 to the cytoplasm. PLoS One 2013; 8:e62581 [View Article] [PubMed]
    [Google Scholar]
  150. Wang X, Liu Y, Li K, Hao Z. Roles of p53-mediated host–virus interaction in coronavirus infection. IJMS 2023; 24:6371 [View Article]
    [Google Scholar]
  151. Kumar A, Grams TR, Bloom DC, Toth Z. Signaling pathway reporter screen with SARS-CoV-2 proteins identifies nsp5 as a repressor of p53 activity. Viruses 2022; 14:1039 [View Article] [PubMed]
    [Google Scholar]
  152. Su M, Shi D, Xing X, Qi S, Yang D et al. coronavirus porcine epidemic diarrhea virus nucleocapsid protein interacts with p53 to induce cell cycle arrest in s-phase and promotes viral replication. J Virol 2021; 95:e0018721 [View Article] [PubMed]
    [Google Scholar]
  153. Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, Müller MA, Deng W et al. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1. Proc Natl Acad Sci U S A 2016; 113:E5192–201 [View Article] [PubMed]
    [Google Scholar]
  154. Jung YS, Hakem A, Hakem R, Chen X. Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis. Mol Cell Biol 2011; 31:3997–4006 [View Article] [PubMed]
    [Google Scholar]
  155. Choi M, Choi YM, An I-S, Bae S, Jung JH et al. E3 ligase RCHY1 negatively regulates HDAC2. Biochem Biophys Res Commun 2020; 521:37–41 [View Article] [PubMed]
    [Google Scholar]
  156. Wu H, Zeinab RA, Flores ER, Leng RP. Pirh2, a ubiquitin E3 ligase, inhibits p73 transcriptional activity by promoting its ubiquitination. Mol Cancer Res 2011; 9:1780–1790 [View Article] [PubMed]
    [Google Scholar]
  157. Bohgaki M, Hakem A, Halaby MJ, Bohgaki T, Li Q et al. The E3 ligase PIRH2 polyubiquitylates CHK2 and regulates its turnover. Cell Death Differ 2013; 20:812–822 [View Article] [PubMed]
    [Google Scholar]
  158. Laurent EMN, Sofianatos Y, Komarova A, Gimeno J-P, Tehrani PS et al. Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms. Syst Biol 2020 [View Article]
    [Google Scholar]
  159. Ren H, Ma C, Peng H, Zhang B, Zhou L et al. Micronucleus production, activation of DNA damage response and cGAS-STING signaling in syncytia induced by SARS-CoV-2 infection. Biol Direct 2021; 16:20 [View Article] [PubMed]
    [Google Scholar]
  160. Basaran MM, Hazar M, Aydın M, Uzuğ G, Özdoğan İ et al. Effects of COVID-19 disease on DNA damage, oxidative stress and immune responses. Toxics 2023; 11:386 [View Article] [PubMed]
    [Google Scholar]
  161. Gain C, Song S, Angtuaco T, Satta S, Kelesidis T. The role of oxidative stress in the pathogenesis of infections with coronaviruses. Front Microbiol 2022; 13:1111930 [View Article] [PubMed]
    [Google Scholar]
  162. Suhail S, Zajac J, Fossum C, Lowater H, McCracken C et al. Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) infection: a review. Protein J 2020; 39:644–656 [View Article] [PubMed]
    [Google Scholar]
  163. Youn JY, Zhang Y, Wu Y, Cannesson M, Cai H. Therapeutic application of estrogen for COVID-19: attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells. Redox Biol 2021; 46:102099 [View Article] [PubMed]
    [Google Scholar]
  164. Hati S, Bhattacharyya S. Impact of thiol-disulfide balance on the binding of covid-19 spike protein with angiotensin-converting enzyme 2 receptor. ACS Omega 2020; 5:16292–16298 [View Article] [PubMed]
    [Google Scholar]
  165. Fossum CJ, Laatsch BF, Lowater HR, Narkiewicz-Jodko AW, Lonzarich L et al. Pre-existing oxidative stress creates a docking-ready conformation of the SARS-CoV-2 receptor-binding domain. ACS Bio Med Chem Au 2022; 2:84–93 [View Article] [PubMed]
    [Google Scholar]
  166. Chen I-Y, Moriyama M, Chang M-F, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol 2019; 10:50 [View Article] [PubMed]
    [Google Scholar]
  167. Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun 2020; 11:4938 [View Article]
    [Google Scholar]
  168. Zhang S, Wang J, Wang L, Aliyari S, Cheng G. SARS-CoV-2 virus NSP14 Impairs NRF2/HMOX1 activation by targeting Sirtuin 1. Cell Mol Immunol 2022; 19:872–882 [View Article]
    [Google Scholar]
  169. Saheb Sharif-Askari N, Saheb Sharif-Askari F, Mdkhana B, Hussain Alsayed HA, Alsafar H et al. Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection. Free Radic Biol Med 2021; 172:688–698 [View Article] [PubMed]
    [Google Scholar]
  170. Berquist BR, Wilson DM III. Pathways for repairing and tolerating the spectrum of oxidative DNA lesions. Cancer Letters 2012; 327:61–72 [View Article]
    [Google Scholar]
  171. Lorente L, Martín MM, González-Rivero AF, Pérez-Cejas A, Cáceres JJ et al. DNA and RNA oxidative damage and mortality of patients With COVID-19. Am J Med Sci 2021; 361:585–590 [View Article] [PubMed]
    [Google Scholar]
  172. Olsen MB, Huse C, de Sousa MML, Murphy SL, Sarno A et al. DNA repair mechanisms are activated in circulating lymphocytes of hospitalized covid-19 patients. J Inflamm Res 2022; 15:6629–6644 [View Article] [PubMed]
    [Google Scholar]
  173. Bakadia BM, Boni BOO, Ahmed AAQ, Yang G. The impact of oxidative stress damage induced by the environmental stressors on COVID-19. Life Sciences 2021; 264:118653 [View Article]
    [Google Scholar]
  174. Mekawy AS, Alaswad Z, Ibrahim AA, Mohamed AA, AlOkda A et al. The consequences of viral infection on host DNA damage response: a focus on SARS-CoVs. J Genet Eng Biotechnol 2022; 20:104 [View Article] [PubMed]
    [Google Scholar]
  175. Victor J, Deutsch J, Whitaker A, Lamkin EN, March A et al. SARS-CoV-2 triggers DNA damage response in Vero E6 cells. Biochem Biophys Res Commun 2021; 579:141–145 [View Article] [PubMed]
    [Google Scholar]
  176. Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S et al. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science 2020; 370:6521 [View Article]
    [Google Scholar]
  177. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 2020; 583:459–468 [View Article] [PubMed]
    [Google Scholar]
  178. Meyers JM, Ramanathan M, Shanderson RL, Beck A, Donohue L et al. The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation. PLoS Pathog 2021; 17:e1009412 [View Article] [PubMed]
    [Google Scholar]
  179. Samavarchi-Tehrani P, Abdouni H, Knight JDR, Astori A, Samson R et al. A SARS-CoV-2 – host proximity interactome. bioRxiv 2020 [View Article]
    [Google Scholar]
  180. Zhou Y, Liu Y, Gupta S, Paramo MI, Hou Y et al. A comprehensive SARS-CoV-2–human protein–protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nat Biotechnol 2023; 41:128–139 [View Article]
    [Google Scholar]
  181. Li J, Guo M, Tian X, Wang X, Yang X et al. Virus-host interactome and proteomic survey reveal potential virulence factors influencing SARS-CoV-2 pathogenesis. Med 2021; 2:99–112 [View Article]
    [Google Scholar]
  182. Liu X, Huuskonen S, Laitinen T, Redchuk T, Bogacheva M et al. SARS-CoV-2-host proteome interactions for antiviral drug discovery. Mol Syst Biol 2021; 17:e10396 [View Article] [PubMed]
    [Google Scholar]
  183. Li G, Tang Z, Fan W, Wang X, Huang L et al. Atlas of interactions between SARS-CoV-2 macromolecules and host proteins. Cell Insight 2023; 2:100068 [View Article] [PubMed]
    [Google Scholar]
  184. Kim D-K, Weller B, Lin C-W, Sheykhkarimli D, Knapp JJ et al. A proteome-scale map of the SARS-CoV-2-human contactome. Nat Biotechnol 2023; 41:140–149 [View Article] [PubMed]
    [Google Scholar]
  185. Duhan N, Kaundal R. HuCoPIA: an atlas of human vs. SARS-CoV-2 interactome and the comparative analysis with other Coronaviridae family viruses. Viruses 2023; 15:492 [View Article] [PubMed]
    [Google Scholar]
  186. Nicolas E, Golemis EA, Arora S. POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene 2016; 590:128–141 [View Article] [PubMed]
    [Google Scholar]
  187. Lipskaia L, Maisonnasse P, Fouillade C, Sencio V, Pascal Q et al. Evidence that SARS-CoV-2 induces lung Cell senescence: potential impact on COVID-19 lung disease. Am J Respir Cell Mol Biol 2022; 66:107–111 [View Article] [PubMed]
    [Google Scholar]
  188. D’Agnillo F, Walters K-A, Xiao Y, Sheng Z-M, Scherler K et al. Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19. Sci Transl Med 2021; 13:620 [View Article] [PubMed]
    [Google Scholar]
  189. Kanakkanthara A, Huntoon CJ, Hou X, Zhang M, Heinzen EP et al. ZC3H18 specifically binds and activates the BRCA1 promoter to facilitate homologous recombination in ovarian cancer. Nat Commun 2019; 10: [View Article]
    [Google Scholar]
  190. Garcia G, Jr Sharma A, Ramaiah A, Sen C, Purkayastha A et al. Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication. Cell Reports 2021; 35:108940 [View Article]
    [Google Scholar]
  191. Sui C, Xiao T, Zhang S, Zeng H, Zheng Y et al. SARS-CoV-2 NSP13 inhibits type I IFN production by degradation of TBK1 via p62-dependent selective autophagy. J Immunol 2022; 208:753–761 [View Article] [PubMed]
    [Google Scholar]
  192. Vazquez C, Swanson SE, Negatu SG, Dittmar M, Miller J et al. SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms. PLoS One 2021; 16:e0253089 [View Article] [PubMed]
    [Google Scholar]
  193. Michelini F, Pitchiaya S, Vitelli V, Sharma S, Gioia U et al. Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nat Cell Biol 2017; 19:1400–1411 [View Article] [PubMed]
    [Google Scholar]
  194. Pessina F, Giavazzi F, Yin Y, Gioia U, Vitelli V et al. Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors. Nat Cell Biol 2019; 21:1286–1299 [View Article] [PubMed]
    [Google Scholar]
  195. Savastano A, Ibáñez de Opakua A, Rankovic M, Zweckstetter M. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nat Commun 2020; 11:6041 [View Article] [PubMed]
    [Google Scholar]
  196. Perdikari TM, Murthy AC, Ryan VH, Watters S, Naik MT et al. SARS‐CoV‐2 nucleocapsid protein phase‐separates with RNA and with human hnRNPs. EMBO J 2020; 39:24 [View Article]
    [Google Scholar]
  197. Curtin N, Bányai K, Thaventhiran J, Le Quesne J, Helyes Z et al. Repositioning PARP inhibitors for SARS‐CoV‐2 infection(COVID‐19); a new multi‐pronged therapy for acute respiratory distress syndrome?. Br J Pharmacol 2020; 177:3635–3645 [View Article]
    [Google Scholar]
  198. Heer CD, Sanderson DJ, Voth LS, Alhammad YMO, Schmidt MS et al. Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. J Biol Chem 2020; 295:17986–17996 [View Article] [PubMed]
    [Google Scholar]
  199. Stone NE, Jaramillo SA, Jones AN, Vazquez AJ, Martz M et al. Stenoparib, an inhibitor of cellular poly(ADP-Ribose) polymerase, blocks replication of the SARS-CoV-2 and HCoV-NL63 human coronaviruses In Vitro. mBio 2021; 12:e03495-20 [View Article] [PubMed]
    [Google Scholar]
  200. Pascal JM. The comings and goings of PARP-1 in response to DNA damage. DNA Repair 2018; 71:177–182 [View Article] [PubMed]
    [Google Scholar]
  201. Langelier MF, Eisemann T, Riccio AA, Pascal JM. PARP family enzymes: regulation and catalysis of the poly(ADP-ribose) posttranslational modification. Curr Opin Struct Biol 2018; 53:187–198 [View Article] [PubMed]
    [Google Scholar]
  202. Cohen MS. Interplay between compartmentalized NAD + synthesis and consumption: A focus on the PARP family. Genes Dev 2020; 34:254–262 [View Article]
    [Google Scholar]
  203. Rampogu S, Jung TS, Ha MW, Lee KW. Repurposing and computational design of PARP inhibitors as SARS-CoV-2 inhibitors. Sci Rep 2023; 13: [View Article]
    [Google Scholar]
  204. Yang W, Kandula S, Huynh M, Greene SK, Van Wye G et al. Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis. Lancet Infect Dis 2021; 21:203–212 [View Article] [PubMed]
    [Google Scholar]
  205. Tsilingiris D, Tentolouris A, Eleftheriadou I, Tentolouris N. Telomere length, epidemiology and pathogenesis of severe COVID-19. Eur J Clin Invest 2020; 50:e13376 [View Article] [PubMed]
    [Google Scholar]
  206. Aviv A. Telomeres and COVID-19. FASEB J 2020; 34:7247–7252 [View Article] [PubMed]
    [Google Scholar]
  207. Mahmoodpoor A, Sanaie S, Roudbari F, Sabzevari T, Sohrabifar N et al. Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity. Gene 2022; 811:146069 [View Article] [PubMed]
    [Google Scholar]
  208. Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco MA. Shorter telomere lengths in patients with severe COVID-19 disease. Aging 2021; 13:1–15 [View Article] [PubMed]
    [Google Scholar]
  209. Xu W, Zhang F, Shi Y, Chen Y, Shi B et al. Causal association of epigenetic aging and COVID-19 severity and susceptibility: a bidirectional Mendelian randomization study. Front Med 2022; 9:989950 [View Article] [PubMed]
    [Google Scholar]
  210. Haridoss M, Ayyasamy L, Bagepally BS. Is COVID-19 severity associated with telomere length? A systematic review and meta-analysis. Virus Genes 2023; 59:489–498 [View Article] [PubMed]
    [Google Scholar]
  211. Benetos A, Lai T-P, Toupance S, Labat C, Verhulst S et al. The nexus between telomere length and lymphocyte count in seniors hospitalized with COVID-19. J Gerontol A Biol Sci Med Sci 2021; 76:e97–e101 [View Article] [PubMed]
    [Google Scholar]
  212. McGroder CF, Zhang D, Choudhury MA, Salvatore MM, D’Souza BM et al. Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax 2021; 76:1242–1245 [View Article]
    [Google Scholar]
  213. Sepe S, Rossiello F, Cancila V, Iannelli F, Matti V et al. DNA damage response at telomeres boosts the transcription of SARS‐CoV‐2 receptor ACE2 during aging. EMBO Reports 2022; 23: [View Article]
    [Google Scholar]
  214. Tong AS, Stern JL, Sfeir A, Kartawinata M, de Lange T et al. ATM and ATR signaling regulate the recruitment of human telomerase to telomeres. Cell Reports 2015; 13:1633–1646 [View Article]
    [Google Scholar]
  215. d’Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 2008; 8:512–522 [View Article]
    [Google Scholar]
  216. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O et al. Cellular senescence: defining a path forward. Cell 2019; 179:813–827 [View Article] [PubMed]
    [Google Scholar]
  217. Schmitt CA, Tchkonia T, Niedernhofer LJ, Robbins PD, Kirkland JL et al. COVID-19 and cellular senescence. Nat Rev Immunol 2023; 23:251–263 [View Article] [PubMed]
    [Google Scholar]
  218. Lee S, Yu Y, Trimpert J, Benthani F, Mairhofer M et al. Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature 2021; 599:283–289 [View Article] [PubMed]
    [Google Scholar]
  219. Evangelou K, Veroutis D, Paschalaki K, Foukas PG, Lagopati N et al. Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis. Eur Respir J 2022; 60:2102951 [View Article] [PubMed]
    [Google Scholar]
  220. Mårtensson CU, Priesnitz C, Song J, Ellenrieder L, Doan KN et al. Mitochondrial protein translocation-associated degradation. Nature 2019; 569:679–683 [View Article] [PubMed]
    [Google Scholar]
  221. Shang C, Liu Z, Zhu Y, Lu J, Ge C et al. SARS-CoV-2 causes mitochondrial dysfunction and mitophagy impairment. Front Microbiol 2021; 12:780768 [View Article] [PubMed]
    [Google Scholar]
  222. Li X, Hou P, Ma W, Wang X, Wang H et al. SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy. Cell Mol Immunol 2022; 19:67–78 [View Article]
    [Google Scholar]
  223. Perumal R, Shunmugam L, Naidoo K, Wilkins D, Garzino-Demo A et al. Biological mechanisms underpinning the development of long COVID. iScience 2023; 26:106935 [View Article]
    [Google Scholar]
  224. Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D et al. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol 2023; 14:1117464 [View Article] [PubMed]
    [Google Scholar]
  225. Astin R, Banerjee A, Baker MR, Dani M, Ford E et al. Long COVID: mechanisms, risk factors and recovery. Exp Physiol 2023; 108:12–27 [View Article] [PubMed]
    [Google Scholar]
  226. Oronsky B, Larson C, Hammond TC, Oronsky A, Kesari S et al. A review of persistent post-COVID syndrome (PPCS). Clin Rev Allergy Immunol 2023; 64:66–74 [View Article] [PubMed]
    [Google Scholar]
  227. Chen B, Julg B, Mohandas S, Bradfute SB. RECOVER mechanistic pathways task force. viral persistence, reactivation, and mechanisms of long COVID. Elife 2023; 12: [View Article]
    [Google Scholar]
  228. Brodin P, Casari G, Townsend L, O’Farrelly C, Tancevski I et al. Studying severe long COVID to understand post-infectious disorders beyond COVID-19. Nat Med 2022; 28:879–882 [View Article] [PubMed]
    [Google Scholar]
  229. Stein SR, Ramelli SC, Grazioli A, Chung J-Y, Singh M et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature 2022; 612:758–763 [View Article]
    [Google Scholar]
  230. Qian Q, Fan L, Liu W, Li J, Yue J et al. Direct evidence of active SARS-CoV-2 replication in the intestine. Clin Infect Dis 2021; 73:361–366 [View Article] [PubMed]
    [Google Scholar]
  231. Xiang Q, Feng Z, Diao B, Tu C, Qiao Q et al. SARS-CoV-2 induces lymphocytopenia by promoting inflammation and decimates secondary lymphoid organs. Front Immunol 2021; 12:661052 [View Article] [PubMed]
    [Google Scholar]
  232. Gaspar-Rodríguez A, Padilla-González A, Rivera-Toledo E. Coronavirus persistence in human respiratory tract and cell culture: an overview. Braz J Infect Dis 2021; 25:101632 [View Article] [PubMed]
    [Google Scholar]
  233. Gaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S et al. Evolution of antibody immunity to SARS-CoV-2. Nature 2021; 591:639–644 [View Article] [PubMed]
    [Google Scholar]
  234. Li N, Wang X, Lv T. Prolonged SARS-CoV-2 RNA shedding: not a rare phenomenon. J Med Virol 2020; 92:2286–2287 [View Article] [PubMed]
    [Google Scholar]
  235. Chen B, Julg B, Mohandas S, Bradfute SB. RECOVER mechanistic pathways task force. viral persistence, reactivation, and mechanisms of long COVID. Elife 2023; 12: [View Article]
    [Google Scholar]
  236. Chen Z, Hu J, Liu L, Chen R, Wang M et al. SARS-CoV-2 causes acute kidney injury by directly infecting renal tubules. Front Cell Dev Biol 2021; 9:664868 [View Article] [PubMed]
    [Google Scholar]
  237. Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J et al. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe 2021; 2:e13–e22 [View Article] [PubMed]
    [Google Scholar]
  238. Tejerina F, Catalan P, Rodriguez-Grande C, Adan J, Rodriguez-Gonzalez C et al. Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19. BMC Infect Dis 2022; 22:211 [View Article] [PubMed]
    [Google Scholar]
  239. Cheung CCL, Goh D, Lim X, Tien TZ, Lim JCT et al. Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19. Gut 2022; 71:226–229 [View Article] [PubMed]
    [Google Scholar]
  240. Zhang L. Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues. Proc Natl Acad Sci USA 2021; 118:21 [View Article]
    [Google Scholar]
  241. Briggs E, Ward W, Rey S, Law D, Nelson K et al. Assessment of potential SARS-CoV-2 virus integration into human genome reveals no significant impact on RT-qPCR COVID-19 testing. Proc Natl Acad Sci U S A 2021; 118:44 [View Article] [PubMed]
    [Google Scholar]
  242. Parry R, Gifford RJ, Lytras S, Ray SC, Coin LJM. No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues. Proc Natl Acad Sci U S A 2021; 118:33 [View Article] [PubMed]
    [Google Scholar]
  243. Mahmood S, Kawanaka M, Kamei A, Izumi A, Nakata K et al. Immunohistochemical evaluation of oxidative stress markers in chronic hepatitis C. Antioxid Redox Signal 2004; 6:19–24 [View Article] [PubMed]
    [Google Scholar]
  244. Konishi M, Iwasa M, Araki J, Kobayashi Y, Katsuki A et al. Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane. J Gastroenterol Hepatol 2006; 21:1821–1825 [View Article] [PubMed]
    [Google Scholar]
  245. Farinati F, Cardin R, Bortolami M, Burra P, Russo FP et al. Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma. J Viral Hepat 2007; 14:821–829 [View Article] [PubMed]
    [Google Scholar]
  246. Machida K, Cheng KT-N, Sung VM-H, Shimodaira S, Lindsay KL et al. Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A 2004; 101:4262–4267 [View Article] [PubMed]
    [Google Scholar]
  247. Machida K, Cheng KT-H, Sung VM-H, Lee KJ, Levine AM et al. Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes. J Virol 2004; 78:8835–8843 [View Article] [PubMed]
    [Google Scholar]
  248. Machida T, Takahashi T, Itoh T, Hirayama M, Morita T et al. Reactive lymphoid hyperplasia of the liver: a case report and review of literature. World J Gastroenterol 2007; 13:5403–5407 [View Article] [PubMed]
    [Google Scholar]
  249. Machida K, Cheng KT-H, Lai C-K, Jeng K-S, Sung VM-H et al. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J Virol 2006; 80:7199–7207 [View Article] [PubMed]
    [Google Scholar]
  250. Machida K, Cheng KTH, Sung VM-H, Levine AM, Foung S et al. Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6. J Virol 2006; 80:866–874 [View Article] [PubMed]
    [Google Scholar]
  251. Higgs MR, Chouteau P, Lerat H. “Liver let die”: oxidative DNA damage and hepatotropic viruses. J Gen Virol 2014; 95:991–1004 [View Article] [PubMed]
    [Google Scholar]
  252. Nikitin PA, Luftig MA. At a crossroads: human DNA tumor viruses and the host DNA damage response. Future Virol 2011; 6:813–830 [View Article] [PubMed]
    [Google Scholar]
  253. Tardivat Y, Sosnowski P, Tidu A, Westhof E, Eriani G et al. SARS-CoV-2 NSP1 induces mRNA cleavages on the ribosome. Nucleic Acids Res 2023; 51:8677–8690 [View Article] [PubMed]
    [Google Scholar]
  254. Schubert K, Karousis ED, Jomaa A, Scaiola A, Echeverria B et al. SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Nat Struct Mol Biol 2020; 27:1094 [View Article] [PubMed]
    [Google Scholar]
  255. Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Science 2020; 369:1249–1255 [View Article]
    [Google Scholar]
  256. Xu Z, Choi J-H, Dai DL, Luo J, Ladak RJ et al. SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation. Proc Natl Acad Sci U S A 2022; 119:e2204539119 [View Article] [PubMed]
    [Google Scholar]
  257. Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A et al. CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes. bioRxiv 2021; 2021:2021 [View Article] [PubMed]
    [Google Scholar]
  258. Li P, Xue B, Schnicker NJ, Wong L-YR, Meyerholz DK et al. Nsp3-N interactions are critical for SARS-CoV-2 fitness and virulence. Proc Natl Acad Sci USA 2023; 120:31 [View Article]
    [Google Scholar]
  259. Armstrong LA, Lange SM, Dee Cesare V, Matthews SP, Nirujogi RS et al. Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies. PLoS One 2021; 16:e0253364 [View Article] [PubMed]
    [Google Scholar]
  260. Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio 2013; 4:e00524-13 [View Article] [PubMed]
    [Google Scholar]
  261. Liu Y, Qin C, Rao Y, Ngo C, Feng JJ et al. SARS-CoV-2 Nsp5 demonstrates two distinct mechanisms targeting RIG-I and MAVS to evade the innate immune response. mBio 2021; 12:e0233521 [View Article] [PubMed]
    [Google Scholar]
  262. Ricciardi S, Guarino AM, Giaquinto L, Polishchuk EV, Santoro M et al. The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle. Nature 2022; 606:761–768 [View Article] [PubMed]
    [Google Scholar]
  263. Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D et al. Structure of replicating SARS-CoV-2 polymerase. Nature 2020; 584:154–156 [View Article] [PubMed]
    [Google Scholar]
  264. Wang Q, Wu J, Wang H, Gao Y, Liu Q et al. Structural basis for RNA replication by the SARS-CoV-2 polymerase. Cell 2020; 182:417–428 [View Article] [PubMed]
    [Google Scholar]
  265. Deng J, Zheng Y, Zheng S-N, Nan M-L, Han L et al. SARS-CoV-2 NSP7 inhibits type I and III IFN production by targeting the RIG-I/MDA5, TRIF, and STING signaling pathways. J Med Virol 2023; 95:e28561 [View Article] [PubMed]
    [Google Scholar]
  266. Deng J, Zheng S-N, Xiao Y, Nan M-L, Zhang J et al. SARS-CoV-2 NSP8 suppresses type I and III IFN responses by modulating the RIG-I/MDA5, TRIF, and STING signaling pathways. J Med Virol 2023; 95:e28680 [View Article] [PubMed]
    [Google Scholar]
  267. Park GJ, Osinski A, Hernandez G, Eitson JL, Majumdar A et al. The mechanism of RNA capping by SARS-CoV-2. Nature 2022; 609:793–800 [View Article] [PubMed]
    [Google Scholar]
  268. Xiang JS, Mueller JR, Luo E-C, Yee BA, Schafer D et al. Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions. bioRxiv2022.02.21.481223 2022 [View Article] [PubMed]
    [Google Scholar]
  269. El-Kamand S, Du Plessis M-D, Breen N, Johnson L, Beard S et al. A distinct ssDNA/RNA binding interface in the Nsp9 protein from SARS-CoV-2. Proteins 2022; 90:176–185 [View Article] [PubMed]
    [Google Scholar]
  270. Riccio AA, Sullivan ED, Copeland WC. Activation of the SARS-CoV-2 NSP14 3’-5’ exoribonuclease by NSP10 and response to antiviral inhibitors. J Biol Chem 2022; 298:101518 [View Article] [PubMed]
    [Google Scholar]
  271. Klima M, Khalili Yazdi A, Li F, Chau I, Hajian T et al. Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16. Protein Sci 2022; 31:e4395 [View Article] [PubMed]
    [Google Scholar]
  272. Gadhave K, Kumar P, Kumar A, Bhardwaj T, Garg N et al. Conformational dynamics of 13 amino acids long NSP11 of SARS-CoV-2 under membrane mimetics and different solvent conditions. Microb Pathog 2021; 158:105041 [View Article] [PubMed]
    [Google Scholar]
  273. Yin W, Mao C, Luan X, Shen D-D, Shen Q et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 2020; 368:1499–1504 [View Article] [PubMed]
    [Google Scholar]
  274. Yuen C-K, Lam J-Y, Wong W-M, Mak L-F, Wang X et al. SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg Microbes Infect 2020; 9:1418–1428 [View Article] [PubMed]
    [Google Scholar]
  275. Sui C, Xiao T, Zhang S, Zeng H, Zheng Y et al. SARS-CoV-2 NSP13 inhibits type I IFN production by degradation of TBK1 via p62-dependent selective autophagy. J Immunol 2022; 208:753–761 [View Article] [PubMed]
    [Google Scholar]
  276. Imprachim N, Yosaatmadja Y, Newman JA. Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development. Nucleic Acids Res 2023; 51:475–487 [View Article] [PubMed]
    [Google Scholar]
  277. Pan R, Kindler E, Cao L, Zhou Y, Zhang Z et al. N7-methylation of the coronavirus RNA cap is required for maximal virulence by preventing innate immune recognition. mBio 2022; 13:e0366221 [View Article] [PubMed]
    [Google Scholar]
  278. Wilson IM, Frazier MN, Li JL, Randall TA, Stanley RE. Biochemical characterization of emerging SARS-CoV-2 Nsp15 endoribonuclease variants. J Mol Biol 2022; 434:167796 [View Article] [PubMed]
    [Google Scholar]
  279. Russ A, Wittmann S, Tsukamoto Y, Herrmann A, Deutschmann J et al. Nsp16 shields SARS-CoV-2 from efficient MDA5 sensing and IFIT1-mediated restriction. EMBO Rep 2022; 23:e55648 [View Article] [PubMed]
    [Google Scholar]
  280. Vithani N, Ward MD, Zimmerman MI, Novak B, Borowsky JH et al. SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential. Biophys J 2021; 120:2880–2889 [View Article] [PubMed]
    [Google Scholar]
  281. Zheng M, Karki R, Williams EP, Yang D, Fitzpatrick E et al. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol 2021; 22:829–838 [View Article] [PubMed]
    [Google Scholar]
  282. Oh SJ, Shin OS. SARS-CoV-2 nucleocapsid protein targets RIG-I-like receptor pathways to inhibit the induction of interferon response. Cells 2021; 10:530 [View Article] [PubMed]
    [Google Scholar]
  283. Chen K, Xiao F, Hu D, Ge W, Tian M et al. SARS-CoV-2 nucleocapsid protein interacts with RIG-I and represses RIG-mediated IFN-β production. Viruses 2020; 13:47 [View Article] [PubMed]
    [Google Scholar]
  284. Guruprasad L. Human coronavirus spike protein-host receptor recognition. Prog Biophys Mol Biol 2021; 161:39–53 [View Article] [PubMed]
    [Google Scholar]
  285. Wang Q, Zhang Y, Wu L, Niu S, Song C et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020; 181:894–904 [View Article]
    [Google Scholar]
  286. Xu H, Akinyemi IA, Chitre SA, Loeb JC, Lednicky JA et al. SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway. Virology 2022; 568:13–22 [View Article]
    [Google Scholar]
  287. Arshad N, Laurent-Rolle M, Ahmed WS, Hsu JC-C, Mitchell SM et al. SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression. Proc Natl Acad Sci USA 2023; 120: [View Article]
    [Google Scholar]
  288. Castaño-Rodriguez C, Honrubia JM, Gutiérrez-Álvarez J, DeDiego ML, Nieto-Torres JL et al. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. mBio 2018; 9:e02325-17 [View Article] [PubMed]
    [Google Scholar]
  289. Kern DM, Sorum B, Mali SS, Hoel CM, Sridharan S et al. Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs. Nat Struct Mol Biol 2021; 28:573–582 [View Article]
    [Google Scholar]
  290. Siu K, Yuen K, Castano‐Rodriguez C, Ye Z, Yeung M et al. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC. FASEB J 2019; 33:8865–8877 [View Article]
    [Google Scholar]
  291. Nie Y, Mou L, Long Q, Deng D, Hu R et al. SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction. Virus Res 2023; 328:199086 [View Article] [PubMed]
    [Google Scholar]
  292. Ren Y, Shu T, Wu D, Mu J, Wang C et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell Mol Immunol 2020; 17:881–883 [View Article] [PubMed]
    [Google Scholar]
  293. Konno Y, Kimura I, Uriu K, Fukushi M, Irie T et al. SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is increased by a naturally occurring elongation variant. Cell Rep 2020; 32:108185 [View Article] [PubMed]
    [Google Scholar]
  294. Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P et al. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc Natl Acad Sci U S A 2020; 117:28344–28354 [View Article] [PubMed]
    [Google Scholar]
  295. Addetia A, Lieberman NAP, Phung Q, Hsiang T-Y, Xie H et al. SARS-CoV-2 ORF6 disrupts bidirectional nucleocytoplasmic transport through interactions with Rae1 and Nup98. mBio 2021; 12:e00065-21 [View Article] [PubMed]
    [Google Scholar]
  296. Lee J-G, Huang W, Lee H, van de Leemput J, Kane MA et al. Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by selinexor. Cell Biosci 2021; 11:58 [View Article] [PubMed]
    [Google Scholar]
  297. Su CM, Wang L, Yoo D. Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2. Sci Rep 2021; 11:13464 [View Article] [PubMed]
    [Google Scholar]
  298. Hou P, Wang X, Wang H, Wang T, Yu Z et al. The ORF7a protein of SARS-CoV-2 initiates autophagy and limits autophagosome-lysosome fusion via degradation of SNAP29 to promote virus replication. Autophagy 2023; 19:551–569 [View Article] [PubMed]
    [Google Scholar]
  299. García-García T, Fernández-Rodríguez R, Redondo N, de Lucas-Rius A, Zaldívar-López S et al. Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b. iScience 2022; 25:105444 [View Article] [PubMed]
    [Google Scholar]
  300. Flower TG, Buffalo CZ, Hooy RM, Allaire M, Ren X et al. Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein. Proc Natl Acad Sci U S A 2021; 118:e2021785118 [View Article] [PubMed]
    [Google Scholar]
  301. Wu X, Xia T, Shin W-J, Yu K-M, Jung W et al. Viral mimicry of interleukin-17A by SARS-CoV-2 ORF8. mBio 2022; 13:e0040222 [View Article] [PubMed]
    [Google Scholar]
  302. Lin X, Fu B, Yin S, Li Z, Liu H et al. ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway. iScience 2021; 24:102293 [View Article]
    [Google Scholar]
  303. Zhang Y, Chen Y, Li Y, Huang F, Luo B et al. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι. Proc Natl Acad Sci USA 2021; 118:23 [View Article]
    [Google Scholar]
  304. Han L, Zhuang M-W, Deng J, Zheng Y, Zhang J et al. SARS-CoV-2 ORF9b antagonizes type I and III interferons by targeting multiple components of the RIG-I/MDA-5-MAVS, TLR3-TRIF, and cGAS-STING signaling pathways. J Med Virol 2021; 93:5376–5389 [View Article] [PubMed]
    [Google Scholar]
  305. Wu J, Shi Y, Pan X, Wu S, Hou R et al. SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep 2021; 34:108761 [View Article] [PubMed]
    [Google Scholar]
  306. Thorne LG, Bouhaddou M, Reuschl A-K, Zuliani-Alvarez L, Polacco B et al. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature 2022; 604:487–495 [View Article] [PubMed]
    [Google Scholar]
  307. Ayinde KS, Pinheiro GMS, Ramos CHI. Binding of SARS-CoV-2 protein ORF9b to mitochondrial translocase TOM70 prevents its interaction with chaperone HSP90. Biochimie 2022; 200:99–106 [View Article] [PubMed]
    [Google Scholar]
  308. Gao X, Zhu K, Qin B, Olieric V, Wang M et al. Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions. Nat Commun 2021; 12: [View Article]
    [Google Scholar]
  309. Jiang H, Zhang H, Meng Q, Xie J, Li Y et al. SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cell Mol Immunol 2020; 17:998–1000 [View Article]
    [Google Scholar]
  310. Dominguez Andres A, Feng Y, Campos AR, Yin J, Yang C-C et al. SARS-CoV-2 ORF9c is a membrane-associated protein that suppresses antiviral responses in cells. bioRxiv 20202020.08.18.256776 [View Article] [PubMed]
    [Google Scholar]
  311. Han L, Zheng Y, Deng J, Nan M-L, Xiao Y et al. SARS-CoV-2 ORF10 antagonizes STING-dependent interferon activation and autophagy. J Med Virol 2022; 94:5174–5188 [View Article] [PubMed]
    [Google Scholar]
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