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Lv L, Zhang L. Host proviral and antiviral factors for SARS-CoV-2. Virus Genes. 2021;57(6):475-488doi: 10.1007/s11262-021-01869-2.
Lv, L., & Zhang, L. (2021). Host proviral and antiviral factors for SARS-CoV-2. Virus genes, 57(6), 475-488. https://doi.org/10.1007/s11262-021-01869-2
Lv, Lu, and Zhang, Leiliang. "Host proviral and antiviral factors for SARS-CoV-2." Virus genes vol. 57,6 (2021): 475-488. doi: https://doi.org/10.1007/s11262-021-01869-2
Lv L, Zhang L. Host proviral and antiviral factors for SARS-CoV-2. Virus Genes. 2021 Dec;57(6):475-488. doi: 10.1007/s11262-021-01869-2. Epub 2021 Sep 11. PMID: 34510331; PMCID: PMC8435179.
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Virus Genes. 2021 Dec;57(6):475-488. doi: 10.1007/s11262-021-01869-2. Epub 2021 Sep 11.

Host proviral and antiviral factors for SARS-CoV-2.

Virus genes

Lu Lv, Leiliang Zhang

Affiliations

  1. Department of Pathogen Biology, School of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
  2. Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
  3. Department of Pathogen Biology, School of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. [email protected].
  4. Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. [email protected].

PMID: 34510331 PMCID: PMC8435179 DOI: 10.1007/s11262-021-01869-2

Abstract

Throughout the viral life cycle, interplays between cellular host factors and virus determine the infectious capacity of the virus. The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a great threat to human life and health. Extensive studies identified a number of host proviral and antiviral factors for SARS-CoV-2. In this review, we summarize the current understanding of the interplay between SARS-CoV-2 and cellular factors during virus entry and replication. Our review will highlight the future direction of study on the infection and pathogenesis of SARS-CoV-2, as well as novel therapeutic strategies and effective antiviral targets for COVID-19.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: Antiviral factor; COVID-19; Host proviral factor; SARS-CoV-2; Virus entry

References

  1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet 395(10223):497–506 - PubMed
  2. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J (2020) The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med 27(2):taaa021 - PubMed
  3. Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P et al (2020) Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe 27(3):325–328 - PubMed
  4. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395(10224):565–574 - PubMed
  5. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798):270–273 - PubMed
  6. Liang Y, Wang ML, Chien CS, Yarmishyn AA, Yang YP, Lai WY et al (2020) Highlight of immune pathogenic response and hematopathologic effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 infection. Front Immunol 11:1022 - PubMed
  7. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z et al (2020) Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181(4):894-904.e9 - PubMed
  8. Letko M, Marzi A, Munster V (2020) Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 5(4):562–569 - PubMed
  9. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A et al (2020) Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA 117(21):11727–11734 - PubMed
  10. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L et al (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11(1):1620 - PubMed
  11. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM et al (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583(7816):459–468 - PubMed
  12. Schneider WM, Luna JM, Hoffmann HH, Sánchez-Rivera FJ, Leal AA, Ashbrook AW et al (2021) Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks. Cell 184(1):120–32.e14 - PubMed
  13. Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL et al (2020) Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell S0092–8674(20):31392–31401 - PubMed
  14. Daniloski Z, Jordan TX, Wessels HH, Hoagland DA, Kasela S, Legut M et al (2020) Identification of required host factors for SARS-CoV-2 infection in human cells. Cell S0092–8674(20):31394–31395 - PubMed
  15. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA et al (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426(6965):450–454 - PubMed
  16. Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pöhlmann S (2005) Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci USA 102(22):7988–7993 - PubMed
  17. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367(6483):1260–1263 - PubMed
  18. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H et al (2020) Structural basis of receptor recognition by SARS-CoV-2. Nature 581(7807):221–224 - PubMed
  19. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2):271–80.e8 - PubMed
  20. Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M et al (2020) Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181(4):905–13.e7 - PubMed
  21. Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C (2020) The protein expression profile of ACE2 in human tissues. Mol Syst Biol 16(7):e9610 - PubMed
  22. Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M et al (2011) Basigin is a receptor essential for erythrocyte invasion by plasmodium falciparum. Nature 480(7378):534–537 - PubMed
  23. Chen Z, Mi L, Xu J, Yu J, Wang X, Jiang J et al (2005) Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis 191(5):755–760 - PubMed
  24. Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P et al (2020) CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct Target Ther 5(1):283 - PubMed
  25. O’Bryan JP, Frye RA, Cogswell PC, Neubauer A, Kitch B, Prokop C et al (1991) Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol 11(10):5016–5031 - PubMed
  26. Wang S, Qiu Z, Hou Y, Deng X, Xu W, Zheng T et al (2021) AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res 31(2):126–140 - PubMed
  27. Cagno V, Tseligka ED, Jones ST, Tapparel C (2019) Heparan sulfate proteoglycans and viral attachment: true receptors or adaptation bias? Viruses 11(7):596 - PubMed
  28. WuDunn D, Spear PG (1989) Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol 63(1):52–58 - PubMed
  29. Roderiquez G, Oravecz T, Yanagishita M, Bou-Habib DC, Mostowski H, Norcross MA (1995) Mediation of human immunodeficiency virus type 1 binding by interaction of cell surface heparan sulfate proteoglycans with the V3 region of envelope gp120-gp41. J Virol 69(4):2233–2239 - PubMed
  30. Milewska A, Zarebski M, Nowak P, Stozek K, Potempa J, Pyrc K (2014) Human coronavirus NL63 utilizes heparan sulfate proteoglycans for attachment to target cells. J Virol 88(22):13221–13230 - PubMed
  31. Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD et al (2020) SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. Cell 183(4):1043–57.e15 - PubMed
  32. Chu H, Hu B, Huang X, Chai Y, Zhou D, Wang Y et al (2021) Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun 12(1):134 - PubMed
  33. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181(2):281–92.e6 - PubMed
  34. Hoffmann M, Kleine-Weber H, Pöhlmann S (2020) A Multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell 78(4):779–84.e5 - PubMed
  35. Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E (2009) C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci USA 106(38):16157–16162 - PubMed
  36. Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Antón-Plágaro C et al (2020) Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370(6518):861–865 - PubMed
  37. Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N et al (2010) Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction. J Med Chem 53(5):2215–2226 - PubMed
  38. Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S et al (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370(6518):856–860 - PubMed
  39. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M (1996) Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271(5248):518–520 - PubMed
  40. Shen WJ, Azhar S, Kraemer FB (2018) SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol 80:95–116 - PubMed
  41. Bajimaya S, Frankl T, Hayashi T, Takimoto T (2017) Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses. Virology 510:234–241 - PubMed
  42. Osuna-Ramos JF, Reyes-Ruiz JM, Del Ángel RM (2018) The role of host cholesterol during flavivirus infection. Front Cell Infect Microbiol 8:388 - PubMed
  43. Dou X, Li Y, Han J, Zarlenga DS, Zhu W, Ren X et al (2018) Cholesterol of lipid rafts is a key determinant for entry and post-entry control of porcine rotavirus infection. BMC Vet Res 14(1):45 - PubMed
  44. Li GM, Li YG, Yamate M, Li SM, Ikuta K (2007) Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. Microbes Infect 9(1):96–102 - PubMed
  45. Catanese MT, Ansuini H, Graziani R, Huby T, Moreau M, Ball JK et al (2010) Role of scavenger receptor class B type I in hepatitis C virus entry: kinetics and molecular determinants. J Virol 84(1):34–43 - PubMed
  46. Wei C, Wan L, Yan Q, Wang X, Zhang J, Yang X et al (2020) HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nat Metab 2(12):1391–1400 - PubMed
  47. Gu Yunqing, Cao Jun, Zhang Xinyu, Gao Hai, Wang Yuyan, Wang Jia, et al (2020) Interaction network of SARS-CoV-2 with host receptome through spike protein. bioRxiv:2020.09.09.287508 - PubMed
  48. Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L et al (2020) Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 383(6):590–592 - PubMed
  49. Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D, Pott F et al (2020) COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat Biotechnol 38(8):970–979 - PubMed
  50. Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M et al (2020) SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 26(5):681–687 - PubMed
  51. Andersson U, Yang H, Harris H (2018) High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells. Semin Immunol 38:40–48 - PubMed
  52. Andersson U, Ottestad W, Tracey KJ (2020) Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? Mol Med 26(1):42 - PubMed
  53. Simpson J, Loh Z, Ullah MA, Lynch JP, Werder RB, Collinson N et al (2020) Respiratory syncytial virus infection promotes necroptosis and HMGB1 release by airway epithelial cells. Am J Respir Crit Care Med 201(11):1358–1371 - PubMed
  54. Zhu Y, Feng F, Hu G, Wang Y, Yu Y, Zhu Y et al (2021) A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry. Nat Commun 12(1):961 - PubMed
  55. Hoffmann HH, Sánchez-Rivera FJ, Schneider WM, Luna JM, Soto-Feliciano YM, Ashbrook AW et al (2021) Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors. Cell Host Microbe 29(2):267–80.e5 - PubMed
  56. Beeraka NM, Sadhu SP, Madhunapantula SV, Rao Pragada R, Svistunov AA, Nikolenko VN et al (2020) Strategies for targeting SARS CoV-2: small molecule inhibitors-the current status. Front Immunol 11:552925 - PubMed
  57. Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T (2011) A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol 85(2):873–882 - PubMed
  58. Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S (2012) Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol 86(12):6537–6545 - PubMed
  59. Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN et al (2020) SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 181(5):1016–35.e19 - PubMed
  60. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, Duh EJ (2020) ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf 18(4):537–544 - PubMed
  61. Braun E, Sauter D (2019) Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunol 8(8):e1073 - PubMed
  62. Izaguirre G (2019) The proteolytic regulation of virus cell entry by furin and other proprotein convertases. Viruses 11(9):837 - PubMed
  63. Cheng YW, Chao TL, Li CL, Chiu MF, Kao HC, Wang SH et al (2020) Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects. Cell Rep 33(2):1254 - PubMed
  64. Xia S, Lan Q, Su S, Wang X, Xu W, Liu Z et al (2020) The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin. Signal Transduct Target Ther 5(1):92 - PubMed
  65. Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P (2005) Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA 102(33):11876–11881 - PubMed
  66. Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S et al (2006) SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem 281(6):3198–3203 - PubMed
  67. de Lartigue J, Polson H, Feldman M, Shokat K, Tooze SA, Urbé S et al (2009) PIKfyve regulation of endosome-linked pathways. Traffic 10(7):883–893 - PubMed
  68. Rutherford AC, Traer C, Wassmer T, Pattni K, Bujny MV, Carlton JG et al (2006) The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport. J Cell Sci 119:3944–3957 - PubMed
  69. Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D et al (2020) Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proc Natl Acad Sci USA 117(34):20803–20813 - PubMed
  70. She J, Zeng W, Guo J, Chen Q, Bai XC, Jiang Y (2019) Structural mechanisms of phospholipid activation of the human TPC2 channel. eLife 8:e45222 - PubMed
  71. Li P, Gu M, Xu H (2019) Lysosomal ion channels as decoders of cellular signals. Trends Biochem Sci 44(2):110–124 - PubMed
  72. Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N et al (2015) Ebola virus. Two-pore channels control ebola virus host cell entry and are drug targets for disease treatment. Science 347(6225):995–8 - PubMed
  73. Lang CM, Fellerer K, Schwenk BM, Kuhn PH, Kremmer E, Edbauer D et al (2012) Membrane orientation and subcellular localization of transmembrane protein 106B (TMEM106B), a major risk factor for frontotemporal lobar degeneration. J Biol Chem 287(23):19355–19365 - PubMed
  74. Brady OA, Zheng Y, Murphy K, Huang M, Hu F (2013) The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal morphology and function. Hum Mol Genet 22(4):685–695 - PubMed
  75. Nicholson AM, Rademakers R (2016) What we know about TMEM106B in neurodegeneration. Acta Neuropathol 132(5):639–651 - PubMed
  76. Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano KA, Hayashi JM et al (2021) Genetic screens identify host factors for SARS-CoV-2 and common cold coronaviruses. Cell 184(1):106–19.e14 - PubMed
  77. Baggen J, Persoons L, Vanstreels E, Jansen S, Van Looveren D, Boeckx B et al (2021) Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2. Nat Genet 53:435–444 - PubMed
  78. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N et al (2011) Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477(7364):340–343 - PubMed
  79. Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT et al (2017) Loss of TMEM106B ameliorates lysosomal and frontotemporal dementia-related phenotypes in progranulin-deficient mice. Neuron 95(2):281–96.e6 - PubMed
  80. Aubol BE, Jamros MA, McGlone ML, Adams JA (2013) Splicing kinase SRPK1 conforms to the landscape of its SR protein substrate. Biochemistry 52(43):7595–7605 - PubMed
  81. Zhong XY, Ding JH, Adams JA, Ghosh G, Fu XD (2009) Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones. Genes Dev 23(4):482–495 - PubMed
  82. Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC et al (1998) SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. J Cell Biol 140(4):737–750 - PubMed
  83. Takamatsu Y, Krähling V, Kolesnikova L, Halwe S, Lier C, Baumeister S et al (2020) Serine-arginine protein kinase 1 regulates ebola virus transcription. mBio 11(1):e02565-19 - PubMed
  84. Karakama Y, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Nishimura-Sakurai Y et al (2010) Inhibition of hepatitis C virus replication by a specific inhibitor of serine-arginine-rich protein kinase. Antimicrob Agents Chemother 54(8):3179–3186 - PubMed
  85. Gaddy CE, Wong DS, Markowitz-Shulman A, Colberg-Poley AM (2010) Regulation of the subcellular distribution of key cellular RNA-processing factors during permissive human cytomegalovirus infection. J Gen Virol 91:1547–1559 - PubMed
  86. Prescott EL, Brimacombe CL, Hartley M, Bell I, Graham S, Roberts S (2014) Human papillomavirus type 1 E1^E4 protein is a potent inhibitor of the serine-arginine (SR) protein kinase SRPK1 and inhibits phosphorylation of host SR proteins and of the viral transcription and replication regulator E2. J Virol 88(21):12599–12611 - PubMed
  87. Tunnicliffe RB, Hu WK, Wu MY, Levy C, Mould AP, McKenzie EA et al (2019) Molecular mechanism of SR protein kinase 1 inhibition by the herpes virus protein ICP27. mBio 10(5):e02551-19 - PubMed
  88. Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J et al (2002) Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein. J Virol 76(16):8124–8137 - PubMed
  89. Peng TY, Lee KR, Tarn WY (2008) Phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization. FEBS J 275(16):4152–4163 - PubMed
  90. Heaton BE, Trimarco JD, Hamele CE, Harding AT, Tata A, Zhu X, et al (2020) SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2. bioRxiv:2020.08.14.251207 - PubMed
  91. Wang C, Xu H, Lin S, Deng W, Zhou J, Zhang Y et al (2020) GPS 50: an update on the prediction of kinase-specific phosphorylation sites in proteins. Genomics Proteomics Bioinform 18(1):72–80 - PubMed
  92. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M et al (2020) The global phosphorylation landscape of SARS-CoV-2 infection. Cell 182(3):685-712.e19 - PubMed
  93. Backer JM (2016) The intricate regulation and complex functions of the Class III phosphoinositide 3-kinase Vps34. Biochem J 473(15):2251–2271 - PubMed
  94. Feng Z, Xu K, Kovalev N, Nagy PD (2019) Recruitment of Vps34 PI3K and enrichment of PI3P phosphoinositide in the viral replication compartment is crucial for replication of a positive-strand RNA virus. PLoS Path 15(1):e1007530 - PubMed
  95. Liefhebber JM, Hague CV, Zhang Q, Wakelam MJ, McLauchlan J (2014) Modulation of triglyceride and cholesterol ester synthesis impairs assembly of infectious hepatitis C virus. J Biol Chem 289(31):21276–21288 - PubMed
  96. Silvas Jesus A, Jureka Alexander S, Nicolini Anthony M, Chvatal Stacie A, Basler Christopher F (2020) Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication. bioRxiv:2020.07.18.210211 - PubMed
  97. Yuen CK, Wong WM, Mak LF, Wang X, Chu H, Yuen KY et al (2021) Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase. J Med Virol 93(4):2076–2083 - PubMed
  98. Snijder EJ, Limpens RWAL, de Wilde AH, de Jong AWM, Zevenhoven-Dobbe JC, Maier HJ et al (2020) A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis. PLoS Biol 18(6):e3000715 - PubMed
  99. Reggiori F, Monastyrska I, Verheije MH, Calì T, Ulasli M, Bianchi S et al (2010) Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication. Cell Host Microbe 7(6):500–508 - PubMed
  100. Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A et al (2019) SKP2 attenuates autophagy through beclin1-ubiquitination and its inhibition reduces MERS-coronavirus infection. Nat Commun 10(1):5770 - PubMed
  101. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E et al (2014) Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat Cell Biol 16(11):1069–1079 - PubMed
  102. Su L, Zhou L, Chen FJ, Wang H, Qian H, Sheng Y et al (2019) Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites. EMBO J 38(8):e100156 - PubMed
  103. Luo J, Yang H, Song BL (2020) Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol 21(4):225–245 - PubMed
  104. Jones DE, Bevins CL (1992) Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267(32):23216–23225 - PubMed
  105. Ericksen B, Wu Z, Lu W, Lehrer RI (2005) Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother 49(1):269–275 - PubMed
  106. Wang C, Shen M, Gohain N, Tolbert WD, Chen F, Zhang N et al (2015) Design of a potent antibiotic peptide based on the active region of human defensin 5. J Med Chem 58(7):3083–3093 - PubMed
  107. Wang C, Wang S, Li D, Wei DQ, Zhao J, Wang J (2020) Human intestinal defensin 5 inhibits SARS-CoV-2 invasion by cloaking ACE2. Gastroenterology 159(3):1145–7.e4 - PubMed
  108. Niv Y (2020) Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 disease. Med Hypotheses 143:110244 - PubMed
  109. Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw G et al (1993) Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 75(6):1179–1186 - PubMed
  110. Somers WS, Tang J, Shaw GD, Camphausen RT (2000) Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell 103(3):467–479 - PubMed
  111. Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H (2009) Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 15(7):794–797 - PubMed
  112. Liu Y, Fu Y, Wang Q, Li M, Zhou Z, Dabbagh D et al (2019) Proteomic profiling of HIV-1 infection of human CD4 T cells identifies PSGL-1 as an HIV restriction factor. Nat Microbiol 4(5):813–825 - PubMed
  113. He S, Hetrick B, Dabbagh D, Akhrymuk IV, Kehn-Hall K, Freed EO, et al (2020) PSGL-1 blocks SARS-CoV-2 S protein-mediated virus attachment and infection of target cells. bioRxiv:2020.05.01.073387 - PubMed
  114. Fu Y, He S, Waheed AA, Dabbagh D, Zhou Z, Trinité B et al (2020) PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells. Proc Natl Acad Sci USA 117(17):9537–9545 - PubMed
  115. Li W, Hulswit RJG, Widjaja I, Raj VS, McBride R, Peng W et al (2017) Identification of sialic acid-binding function for the middle east respiratory syndrome coronavirus spike glycoprotein. Proc Natl Acad Sci USA 114(40):E8508–E8517 - PubMed
  116. Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE et al (2020) Virus-receptor interactions of glycosylated SARS-CoV-2 spike and human ACE2 receptor. Cell Host Microbe 28(4):586-601.e6 - PubMed
  117. Park A, Iwasaki A (2020) Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe 27(6):870–878 - PubMed
  118. Liu SY, Aliyari R, Chikere K, Li G, Marsden MD, Smith JK et al (2013) Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38(1):92–105 - PubMed
  119. Lund EG, Kerr TA, Sakai J, Li WP, Russell DW (1998) cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J Biol Chem 273(51):34316–34327 - PubMed
  120. Li C, Deng YQ, Wang S, Ma F, Aliyari R, Huang XY et al (2017) 25-Hydroxycholesterol protects host against zika virus infection and its associated microcephaly in a mouse model. Immunity 46(3):446–456 - PubMed
  121. Wang S, Li W, Hui H, Tiwari SK, Zhang Q, Croker BA et al (2020) Cholesterol 25-hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol. EMBO J 39(21):6057 - PubMed
  122. Johnson KA, Endapally S, Vazquez DC, Infante RE, Radhakrishnan A (2019) Ostreolysin A and anthrolysin O use different mechanisms to control movement of cholesterol from the plasma membrane to the endoplasmic reticulum. J Biol Chem 294(46):17289–17300 - PubMed
  123. Abrams ME, Johnson KA, Perelman SS, Zhang LS, Endapally S, Mar KB et al (2020) Oxysterols provide innate immunity to bacterial infection by mobilizing cell surface accessible cholesterol. Nat Microbiol 5(7):929–942 - PubMed
  124. Yu J, Liu SL (2019) Emerging role of LY6E in virus-host interactions. Viruses 11(11):1020 - PubMed
  125. Zhao X, Zheng S, Chen D, Zheng M, Li X, Li G et al (2020) LY6E restricts entry of human coronaviruses, including currently pandemic SARS-CoV-2. J Virol 94(18):e00562-e620 - PubMed
  126. Mar KB, Rinkenberger NR, Boys IN, Eitson JL, McDougal MB, Richardson RB et al (2018) LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step. Nat Commun 9(1):3603 - PubMed
  127. Pfaender S, Mar KB, Michailidis E, Kratzel A, BoysV’kovski INP et al (2020) LY6E impairs coronavirus fusion and confers immune control of viral disease. Nat Microbiol 5(11):1330–1339 - PubMed
  128. Meagher JL, Takata M, Gonçalves-Carneiro D, Keane SC, Rebendenne A, Ong H et al (2019) Structure of the zinc-finger antiviral protein in complex with RNA reveals a mechanism for selective targeting of CG-rich viral sequences. Proc Natl Acad Sci USA 116(48):24303–24309 - PubMed
  129. Ficarelli M, Antzin-Anduetza I, Hugh-White R, Firth AE, Sertkaya H, Wilson H et al (2020) CpG dinucleotides inhibit HIV-1 replication through zinc finger antiviral protein (ZAP)-dependent and -independent mechanisms. J Virol 94(6):e01337-e1419 - PubMed
  130. Takata MA, Gonçalves-Carneiro D, Zang TM, Soll SJ, York A, Blanco-Melo D et al (2017) CG dinucleotide suppression enables antiviral defence targeting non-self RNA. Nature 550(7674):124–127 - PubMed
  131. Woo PC, Wong BH, Huang Y, Lau SK, Yuen KY (2007) Cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape codon usage bias in coronaviruses. Virology 369(2):431–442 - PubMed
  132. Xia X (2020) Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol 37(9):2699–2705 - PubMed
  133. Nchioua R, Kmiec D, Müller JA, Conzelmann C, Groß R, Swanson CM et al (2020) SARS-CoV-2 is restricted by zinc finger antiviral protein despite preadaptation to the low-CpG environment in humans. mBio 11(5):e01930-20 - PubMed
  134. Calcaterra NB, Armas P, Weiner AM, Borgognone M (2010) CNBP: a multifunctional nucleic acid chaperone involved in cell death and proliferation control. IUBMB Life 62(10):707–714 - PubMed
  135. Schmidt N, Lareau CA, Keshishian H, Ganskih S, Schneider C, Hennig T et al (2020) The SARS-CoV-2 RNA-protein interactome in infected human cells. Nat Microbiol 6(3):339–353 - PubMed
  136. Kerns JA, Emerman M, Malik HS (2008) Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet 4(1):e21 - PubMed
  137. Klann K, Bojkova D, Tascher G, Ciesek S, Münch C, Cinatl J (2020) Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication. Mol Cell 80(1):164–74.e4 - PubMed
  138. Fonseca BD, Zakaria C, Jia JJ, Graber TE, Svitkin Y, Tahmasebi S et al (2015) La-related protein 1 (LARP1) represses terminal oligopyrimidine (TOP) mRNA translation downstream of mTOR complex 1 (mTORC1). J Biol Chem 290(26):15996–16020 - PubMed

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