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Introduction to the Virus and Its Infection Stages

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COVID-19

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Abstract

Coronavirus disease 2019 (COVID-19) originated from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which has been affecting numerous people in many countries. Many patients have been involved with various disorders and complications like acute lung injury (ALI) and cytokine storm leading to mortality in severe cases. Consequently, this disaster has propelled scientists and pharmaceutical companies to develop practical vaccines and employ the drug repurposing approach to inhibit the disease. Taking the biology and pathogenesis stages of the SARS-CoV-2 infection into account, it is demonstrated that COVID-19 is associated with direct damages induced by the virus, besides the host inflammatory and immune responses. Accordingly, this chapter is planned to sequentially discuss the biology of SARS-CoV-2 and the stages of the virus pathogenesis.

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References

  1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R (2020) A novel coronavirus from patients with pneumonia in China, 2019. New Engl J Med

    Google Scholar 

  2. M. Nicola, Z. Alsafi, C. Sohrabi, A. Kerwan, A. Al-Jabir, C. Iosifidis, M. Agha, R. Agha, The socio-economic implications of the coronavirus and COVID-19 pandemic: a review. Int J Surg (2020)

    Google Scholar 

  3. Maurya VK, Kumar S, Bhatt ML, Saxena SK (2020) Therapeutic development and drugs for the treatment of COVID-19, coronavirus disease 2019 (COVID-19). Springer, pp 109–126

    Google Scholar 

  4. Tu Y-F, Chien C-S, Yarmishyn AA, Lin Y-Y, Luo Y-H, Lin Y-T, Lai W-Y, Yang D-M, Chou S-J, Yang Y-P (2020) A review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci 21(7):2657

    Article  Google Scholar 

  5. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395(10224):565–574

    Article  Google Scholar 

  6. Singhal T (2020) A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 1–6

    Google Scholar 

  7. Kumar GV, Jeyanthi V, Ramakrishnan S (2020) A short review on antibody therapy for COVID-19. New Microbes New Infect 100682

    Google Scholar 

  8. Harapan H, Itoh N, Yufika A, Winardi W, Keam S, Te H, Megawati D, Hayati Z, Wagner AL, Mudatsir M (2020) Coronavirus disease 2019 (COVID-19): a literature review. J Infect Public Health

    Google Scholar 

  9. Zhou M, Zhang X, Qu J (2020) Coronavirus disease 2019 (COVID-19): a clinical update. Front Med 1–10

    Google Scholar 

  10. Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G (2020) Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 12(4):372

    Article  Google Scholar 

  11. Chen Y, Liu Q, Guo D (2020) Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 92(4):418–423

    Article  Google Scholar 

  12. Lai C-C, Shih T-P, Ko W-C, Tang H-J, Hsueh P-R (2020) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents 105924

    Google Scholar 

  13. Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D, Jin H-J, Tan K-S, Wang D-Y, Yan Y (2020) The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Military Med Res 7(1):1–10

    Article  Google Scholar 

  14. WHO (2021) COVID-19 weekly epidemiological update. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/. Accessed 6 Jan 2021

  15. Sun P, Lu X, Xu C, Sun W, Pan B (2020) Understanding of COVID-19 based on current evidence. J Med Virol 92(6):548–551

    Article  Google Scholar 

  16. Ita K (2020) Coronavirus DIsease (COVID-19): current status and prospects for drug and vaccine development. Arch Med Res

    Google Scholar 

  17. Giovane RA, Rezai S, Cleland E, Henderson CE (2020) Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID-19) and the rationale for their utilization: a review. Rev Med Virol 30(5):

    Article  Google Scholar 

  18. Jamwal S, Gautam A, Elsworth J, Kumar M, Chawla R, Kumar P (2020) An updated insight into the molecular pathogenesis, secondary complications and potential therapeutics of COVID-19 pandemic. Life Sci 118105

    Google Scholar 

  19. Chary MA, Barbuto AF, Izadmehr S, Hayes BD, Burns MM (2020) COVID-19: therapeutics and their toxicities. J Med Toxicol 16(3):101007

    Google Scholar 

  20. Wu R, Wang L, Kuo H-CD, Shannar A, Peter R, Chou PJ, Li S, Hudlikar R, Liu X, Liu Z (2020) An update on current therapeutic drugs treating COVID-19. Curr Pharmacol Rep 1

    Google Scholar 

  21. Salvi R, Patankar P (2020) Emerging pharmacotherapies for COVID-19. Biomed Pharmacotherapy 110267

    Google Scholar 

  22. Zhang Y, Xu Q, Sun Z, Zhou L (2020) Current targeted therapeutics against COVID-19: based on first-line experience in china. Pharmacol Res 104854

    Google Scholar 

  23. Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A, Govindasamy V, Giridharan B, Ganesan S, Venugopal A, Venkatesan D, Ganesan H (2020) COVID-19: a promising cure for the global panic. Sci Total Environ 138277

    Google Scholar 

  24. Sohrabi C, Alsafi Z, O’Neill N, Khan M, Kerwan A, Al-Jabir A, Iosifidis C, Agha R (2020) World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19). Int J Surg

    Google Scholar 

  25. Taylor D (2015) The pharmaceutical industry and the future of drug development

    Google Scholar 

  26. Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK (2020) Drug repurposing approach to fight COVID-19. Pharmacol Rep 1–30

    Google Scholar 

  27. Shah B, Modi P, Sagar SR (2020) In silico studies on therapeutic agents for COVID-19: drug repurposing approach. Life Sci 117652

    Google Scholar 

  28. Alnefaie A, Albogami S (2020) Current approaches used in treating COVID-19 from a molecular mechanisms and immune response perspective. Saudi Pharm J

    Google Scholar 

  29. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (2020) Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 323(18):1824–1836

    Google Scholar 

  30. Xian Y, Zhang J, Bian Z, Zhou H, Zhang Z, Lin Z, Xu H (2020) Bioactive natural compounds against human coronaviruses: a review and perspective. Acta Pharmaceutica Sinica B

    Google Scholar 

  31. Artika IM, Dewantari AK, Wiyatno A (2020) Molecular biology of coronaviruses: current knowledge. Heliyon e04743

    Google Scholar 

  32. C.S.G. of the International (2020) The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 5(4):536

    Google Scholar 

  33. Paules CI, Marston HD, Fauci AS (2020) Coronavirus infections—more than just the common cold. JAMA 323(8):707–708

    Article  Google Scholar 

  34. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, Dhama K, Yatoo MI, Bonilla-Aldana DK, Rodriguez-Morales AJ (2020) SARS-CoV-2, SARS-CoV, and MERS-CoV: a comparative overview. Infez Med 28(2):174–184

    Google Scholar 

  35. V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V (2020) Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 1–16

    Google Scholar 

  36. Wang L-S, Wang Y-R, Ye D-W, Liu Q-Q (2020) A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. Int J Antimicrob Agents 105948

    Google Scholar 

  37. Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E (2020) COVID-19, SARS and MERS: are they closely related? Clin Microbiol Infect (2020)

    Google Scholar 

  38. L. Mousavizadeh, S. Ghasemi, Genotype and phenotype of COVID-19: Their roles in pathogenesis, Journal of Microbiology, Immunology and Infection (2020)

    Google Scholar 

  39. van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ (2012) Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 3(6)

    Google Scholar 

  40. Masters PS (2006) The molecular biology of coronaviruses. Adv Virus Res 66:193–292

    Article  Google Scholar 

  41. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11(1):1–12

    Article  ADS  Google Scholar 

  42. Tortorici MA, Walls AC, Lang Y, Wang C, Li Z, Koerhuis D, Boons G-J, Bosch B-J, Rey FA, de Groot RJ (2019) Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol 26(6):481–489

    Article  Google Scholar 

  43. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F (2020) Structural basis of receptor recognition by SARS-CoV-2. Nature 581(7807):221–224

    Article  ADS  Google Scholar 

  44. Hulswit R, De Haan C, Bosch B-J (2016) Coronavirus spike protein and tropism changes. Adv Virus Res 29–57

    Google Scholar 

  45. Kuo L, Hurst KR, Masters PS (2007) Exceptional flexibility in the sequence requirements for coronavirus small envelope protein function. J Virol 81(5):2249–2262

    Article  Google Scholar 

  46. Schoeman D, Fielding BC (2019) Coronavirus envelope protein: current knowledge. Virol J 16(1):1–22

    Article  Google Scholar 

  47. Du Y, Zuckermann FA, Yoo D (2010) Myristoylation of the small envelope protein of porcine reproductive and respiratory syndrome virus is non-essential for virus infectivity but promotes its growth. Virus Res 147(2):294–299

    Article  Google Scholar 

  48. Ruch TR, Machamer CE (2012) The coronavirus E protein: assembly and beyond. Viruses 4(3):363–382

    Article  Google Scholar 

  49. Heinz F, Collett M, Purcell R, Gould E, Howard C, Van Regenmortel MHV, Fauquet CM, Bishop DHL, Carstens EB, Estes MK et al (2000) Virus taxonomy. In: Seventh Report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego, pp 859–878

    Google Scholar 

  50. Wu Q, Zhang Y, Lü H, Wang J, He X, Liu Y, Ye C, Lin W, Hu J, Ji J (2003) The E protein is a multifunctional membrane protein of SARS-CoV. Genom Proteomics Bioinformatics 1(2):131–144

    Article  Google Scholar 

  51. McClenaghan C, Hanson A, Lee S-J, Nichols CG (2020) Coronavirus proteins as Ion channels: current and potential research. Front Immunol 11:2651

    Article  Google Scholar 

  52. Sarkar M, Saha S (2020) Structural insight into the role of novel SARS-CoV-2 E protein: a potential target for vaccine development and other therapeutic strategies. PLoS ONE 15(8):

    Article  Google Scholar 

  53. Ujike M, Taguchi F (2015) Incorporation of spike and membrane glycoproteins into coronavirus virions. Viruses 7(4):1700–1725

    Article  Google Scholar 

  54. De Haan CA, Smeets M, Vernooij F, Vennema H, Rottier P (1999) Mapping of the coronavirus membrane protein domains involved in interaction with the spike protein. J Virol 73(9):7441–7452

    Article  Google Scholar 

  55. Arndt AL, Larson BJ, Hogue BG (2010) A conserved domain in the coronavirus membrane protein tail is important for virus assembly. J Virol 84(21):11418–11428

    Article  Google Scholar 

  56. Thomas S (2020) The structure of the membrane protein of SARS-CoV-2 resembles the sugar transporter semiSWEET

    Google Scholar 

  57. Chang C-K, Hou M-H, Chang C-F, Hsiao C-D, Huang T-H (2014) The SARS coronavirus nucleocapsid protein–forms and functions. Antiviral Res 103:39–50

    Article  Google Scholar 

  58. Dutta NK, Mazumdar K, Gordy JT (2020) The nucleocapsid protein of SARS–CoV-2: a target for vaccine development. J Virol 94(13)

    Google Scholar 

  59. Wurm T, Chen H, Hodgson T, Britton P, Brooks G, Hiscox JA (2001) Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. J Virol 75(19):9345–9356

    Article  Google Scholar 

  60. Surjit M, Liu B, Chow VT, Lal SK (2006) 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 281(16):10669–10681

    Article  Google Scholar 

  61. Mu J, Fang Y, Yang Q, Shu T, Wang A, Huang M, Jin L, Deng F, Qiu Y, Zhou X (2020) SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2. Cell discovery 6(1):1–4

    Article  Google Scholar 

  62. Kopecky-Bromberg SA, Martínez-Sobrido L, Frieman M, Baric RA, Palese P (2007) Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol 81(2):548–557

    Article  Google Scholar 

  63. Yan X, Hao Q, Mu Y, Timani KA, Ye L, Zhu Y, Wu J (2006) Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein. Int J Biochem Cell Biol 38(8):1417–1428

    Article  Google Scholar 

  64. Surjit M, Liu B, Jameel S, Chow VT, Lal SK (2004) The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors. Biochem J 383(1):13–18

    Article  Google Scholar 

  65. Huang Q, Yu L, Petros AM, Gunasekera A, Liu Z, Xu N, Hajduk P, Mack J, Fesik SW, Olejniczak ET (2004) Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein. Biochemistry 43(20):6059–6063

    Article  Google Scholar 

  66. Zeng W, Liu G, Ma H, Zhao D, Yang Y, Liu M, Mohammed A, Zhao C, Yang Y, Xie J (2020) Biochemical characterization of SARS-CoV-2 nucleocapsid protein. Biochem Biophys Res Commun

    Google Scholar 

  67. McBride R, Van Zyl M, Fielding BC (2014) The coronavirus nucleocapsid is a multifunctional protein. Viruses 6(8):2991–3018

    Article  Google Scholar 

  68. Astuti I (2020) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diab Metabolic Synd Clin Res Rev

    Google Scholar 

  69. Subissi L, Imbert I, Ferron F, Collet A, Coutard B, Decroly E, Canard B (2014) SARS-CoV ORF1b-encoded nonstructural proteins 12–16: replicative enzymes as antiviral targets. Antiviral Res 101:122–130

    Article  Google Scholar 

  70. Zhang W, Zhang P, Wang G, Cheng W, Chen J, Zhang X (2020) Recent advances of therapeutic targets and potential drugs of COVID-19. Die Pharmazie Int J Pharm Sci 75(5):160–162

    Google Scholar 

  71. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798):270–273

    Google Scholar 

  72. Michel CJ, Mayer C, Poch O, Thompson JD (2020) Characterization of accessory genes in coronavirus genomes

    Google Scholar 

  73. Liu DX, Fung TS, Chong KK-L, Shukla A, Hilgenfeld R (2014) Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 109:97–109

    Article  Google Scholar 

  74. Kim D, Lee J-Y, Yang J-S, Kim JW, Kim VN, Chang H (2020) The architecture of SARS-CoV-2 transcriptome. Cell

    Google Scholar 

  75. Tang X, Wu C, Li X, Song Y, Yao X, Wu X, Duan Y, Zhang H, Wang Y, Qian Z (2020) On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev

    Google Scholar 

  76. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell

    Google Scholar 

  77. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F (2020) Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci 117(13):7001–7003

    Article  Google Scholar 

  78. Santos IDA, Grosche VR, Bergamini FRG, Sabino-Silva R, Jardim AC (2020) Antivirals against coronaviruses: candidate drugs for SARS-coV-2 treatment? Front Microbiol 11:1818

    Google Scholar 

  79. Depfenhart M, de Villiers D, Lemperle G, Meyer M, Di Somma S (2020) Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy? Internal Emerg Med 1

    Google Scholar 

  80. Tripet B, Howard MW, Jobling M, Holmes RK, Holmes KV, Hodges RS (2004) Structural characterization of the SARS-coronavirus spike S fusion protein core. J Biol Chem 279(20):20836–20849

    Article  Google Scholar 

  81. Li F, Li W, Farzan M, Harrison SC (2005) Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309(5742):1864–1868

    Article  ADS  Google Scholar 

  82. Lip K-M, Shen S, Yang X, Keng C-T, Zhang A, Oh H-LJ, Li Z-H, Hwang L-A, Chou C-F, Fielding BC (2006) Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J Virol 80(2):941–950

    Article  Google Scholar 

  83. Lai S-C, Chong PC-S, Yeh C-T, Liu LS-J, Jan J-T, Chi H-Y, Liu H-W, Chen A, Wang Y-C (2005) Characterization of neutralizing monoclonal antibodies recognizing a 15-residues epitope on the spike protein HR2 region of severe acute respiratory syndrome coronavirus (SARS-CoV). J Biomed Sci 12(5):711–727

    Article  Google Scholar 

  84. Rockx B, Donaldson E, Frieman M, Sheahan T, Corti D, Lanzavecchia A, Baric RS (2010) Escape from human monoclonal antibody neutralization affects in vitro and in vivo fitness of severe acute respiratory syndrome coronavirus. J Infect Dis 201(6):946–955

    Article  Google Scholar 

  85. Zhang H, Wang G, Li J, Nie Y, Shi X, Lian G, Wang W, Yin X, Zhao Y, Qu X (2004) Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies. J Virol 78(13):6938–6945

    Article  Google Scholar 

  86. Keng C-T, Zhang A, Shen S, Lip K-M, Fielding BC, Tan TH, Chou C-F, Loh CB, Wang S, Fu J (2005) Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: implications for the development of vaccines and antiviral agents. J Virol 79(6):3289–3296

    Article  Google Scholar 

  87. Elshabrawy HA, Coughlin MM, Baker SC, Prabhakar BS (2012) Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing. PLoS ONE 7(11):

    Article  ADS  Google Scholar 

  88. Fung TS, Liu DX (2018) Post-translational modifications of coronavirus proteins: roles and function. Future Virol 13(6):405–430

    Article  Google Scholar 

  89. Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L (2020) Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 17(6):613–620

    Article  Google Scholar 

  90. Vaduganathan M, Vardeny O, Michel T, McMurray JJ, Pfeffer MA, Solomon SD (2020) Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med 382(17):1653–1659

    Article  Google Scholar 

  91. Turner AJ (2015) ACE2 cell biology, regulation, and physiological functions. The protective arm of the renin angiotensin system (RAS), p 185

    Google Scholar 

  92. Camargo SM, Vuille-dit-Bille RN, Meier CF, Verrey F (2020) ACE2 and gut amino acid transport. Clin Sci 134(21):2823–2833

    Article  Google Scholar 

  93. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med 11(8):875–879

    Article  Google Scholar 

  94. Imai Y, Kuba K, Penninger JM (2008) The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice. Exp Physiol 93(5):543–548

    Article  Google Scholar 

  95. Sarkar C, Mondal M, Torequl Islam M, Martorell M, Docea AO, Maroyi A, Sharifi-Rad J, Calina D (2020) Potential therapeutic options for COVID-19: current status, challenges, and future perspectives. Front. Pharmacol 11:1428

    Google Scholar 

  96. Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A, Berrino L, Racagni G, Rossi F, Capuano A (2020) Current pharmacological treatments for COVID-19: What’s next? Br J Pharmacol

    Google Scholar 

  97. Luan B, Huynh T, Cheng X, Lan G, Wang H-R (2020) Targeting proteases for treating COVID-19. J Proteome Res 19(11):4316–4326

    Article  Google Scholar 

  98. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell

    Google Scholar 

  99. Ko C-J, Hsu T-W, Wu S-R, Lan S-W, Hsiao T-F, Lin H-Y, Lin H-H, Tu H-F, Lee C-F, Huang C-C (2020) Inhibition of TMPRSS2 by HAI-2 reduces prostate cancer cell invasion and metastasis. Oncogene 39(37):5950–5963

    Article  Google Scholar 

  100. Luan B, Huynh T, Cheng X, Lan G, Wang H-R (2020) Targeting proteases for treating COVID-19. J Proteome Res

    Google Scholar 

  101. Belouzard S, Chu VC, Whittaker GR (2009) Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci 106(14):5871–5876

    Article  ADS  Google Scholar 

  102. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun X-W, Varambally S, Cao X, Tchinda J, Kuefer R (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310(5748):644–648

    Google Scholar 

  103. Hoffmann M, Schroeder S, Kleine-Weber H, Müller MA, Drosten C, Pöhlmann S (2020) Nafamostat mesylate blocks activation of SARS-CoV-2: new treatment option for COVID-19. Antimicrob Agents Chemotherapy

    Google Scholar 

  104. Mikkonen L, Pihlajamaa P, Sahu B, Zhang F-P, Jänne OA (2010) Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol 317(1–2):14–24

    Article  Google Scholar 

  105. Fujimoto T, Tsunedomi R, Matsukuma S, Yoshimura K, Oga A, Fujiwara N, Fujiwara Y, Matsui H, Shindo Y, Tokumitsu Y (2020) Cathepsin B is highly expressed in pancreatic cancer stem-like cells and is associated with patients’ surgical outcomes. Oncol Lett 21(1):1–1

    Article  Google Scholar 

  106. Roshy S, Sloane BF, Moin K (2003) Pericellular cathepsin B and malignant progression. Cancer Metastasis Rev 22(2–3):271–286

    Article  Google Scholar 

  107. Yang N, Shen H-M (2020) Targeting the endocytic pathway and autophagy process as a novel therapeutic strategy in COVID-19. Int J Biol Sci 16(10):1724

    Article  Google Scholar 

  108. Aguiar AC, Murce E, Cortopassi WA, Pimentel AS, Almeida MM, Barros DC, Guedes JS, Meneghetti MR, Krettli AU (2018) Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity. Int J Parasitol Drugs Drug Resistance 8(3):459–464

    Article  Google Scholar 

  109. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M (2020) Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 6(1):1–4

    Article  Google Scholar 

  110. Schrezenmeier E, Dörner T (2020) Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 1–12

    Google Scholar 

  111. Yang J-K, Zhao M-M, Yang W-L, Yang F-Y, Zhang L, Huang W, Fan C, Hou W, Jin R, Feng Y (2020) Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. medRxiv

    Google Scholar 

  112. Zhu Z, Lu Z, Xu T, Chen C, Yang G, Zha T, Lu J, Xue Y (2020) Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19. J Infect 81(1):e21–e23

    Article  Google Scholar 

  113. Cannalire R, Stefanelli I, Cerchia C, Beccari AR, Pelliccia S, Summa V (2020) SARS-CoV-2 entry inhibitors: small molecules and peptides targeting virus or host cells. Int J Mol Sci 21(16):5707

    Article  Google Scholar 

  114. Liu T, Luo S, Libby P, Shi G-P (2020) Cathepsin L-selective inhibitors: a potentially promising treatment for COVID-19 patients. Pharmacol Therap 107587

    Google Scholar 

  115. Fung TS, Liu DX (2019) Human coronavirus: host-pathogen interaction. Annu Rev Microbiol 73:529–557

    Article  Google Scholar 

  116. Van Hemert MJ, Van Den Worm SH, Knoops K, Mommaas AM, Gorbalenya AE, Snijder EJ (2008) SARS-coronavirus replication/transcription complexes are membrane-protected and need a host factor for activity in vitro. PLoS Pathog 4(5):

    Article  Google Scholar 

  117. Qiu Y, Xu K (2020) Functional studies of the coronavirus nonstructural proteins. STEMedicine 1(2):e39–e39

    Article  Google Scholar 

  118. Woo J, Lee EY, Lee M, Kim T, Cho Y-E (2019) An in vivo cell-based assay for investigating the specific interaction between the SARS-CoV N-protein and its viral RNA packaging sequence. Biochem Biophys Res Commun 520(3):499–506

    Article  Google Scholar 

  119. Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S (2020) Coronavirus membrane fusion mechanism offers as a potential target for antiviral development. Antiviral Res 104792

    Google Scholar 

  120. Mitra K, Ghanta P, Acharya S, Chakrapani G, Ramaiah B, Doble M (2020) Dual inhibitors of SARS-CoV-2 proteases: pharmacophore and molecular dynamics based drug repositioning and phytochemical leads. J Biomol Struct Dyn 1–14

    Google Scholar 

  121. Novak J, Rimac H, Kandagalla S, Pathak P, Grishina M, Potemkin V (2020) Proposition of a new allosteric binding site for potential SARS-CoV-2 3CL protease inhibitors by utilizing molecular dynamics simulations and ensemble docking

    Google Scholar 

  122. Oudshoorn D, Rijs K, Limpens RW, Groen K, Koster AJ, Snijder EJ, Kikkert M, Bárcena M (2017) Expression and cleavage of middle east respiratory syndrome coronavirus nsp3-4 polyprotein induce the formation of double-membrane vesicles that mimic those associated with coronaviral RNA replication. MBio 8(6)

    Google Scholar 

  123. Clemente V, D’Arcy P, Bazzaro M (2020) Deubiquitinating enzymes in coronaviruses and possible therapeutic opportunities for COVID-19. Int J Mol Sci 21(10):3492

    Article  Google Scholar 

  124. Ruzicka JA (2020) Identification of the antithrombotic protein S as a potential target of the SARS-CoV-2 papain-like protease. Thromb Res 196:257–259

    Article  Google Scholar 

  125. Huynh T, Wang H, Luan B (2020) In silico exploration of molecular mechanism of clinically oriented drugs for possibly inhibiting SARS-CoV-2’s main protease. J Phys Chem Lett

    Google Scholar 

  126. Lin M-H, Moses DC, Hsieh C-H, Cheng S-C, Chen Y-H, Sun C-Y, Chou C-Y (2018) Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res 150:155–163

    Article  Google Scholar 

  127. Baden LR, Rubin EJ (2020) Covid-19—the search for effective therapy. Mass Medical Soc

    Google Scholar 

  128. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO (2020) Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature communications 11(1):1–14

    Article  Google Scholar 

  129. Qu J-M, Cao B, Chen R-C (2020) Treatment of COVID-19. COVID-19 55

    Google Scholar 

  130. Gaurav A, Al-Nema M (2019) Polymerases of coronaviruses: structure, function, and inhibitors, viral polymerases. Elsevier, pp 271–300

    Google Scholar 

  131. Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368(6492):779–782

    Article  ADS  Google Scholar 

  132. Jiang Y, Yin W, Xu HE (2020) RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochem Biophys Res Commun

    Google Scholar 

  133. Kirchdoerfer RN, Ward AB (2019) Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun 10(1):1–9

    Article  ADS  Google Scholar 

  134. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3):269–271

    Article  Google Scholar 

  135. Martinez MA (2020) Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemotherapy 64(5)

    Google Scholar 

  136. Tao YY, Tang LV, Hu Y (2020) Treatments in the COVID-19 pandemic: an update on clinical trials. Taylor & Francis

    Google Scholar 

  137. Dong L, Hu S, Gao J (2020) Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Therap 14(1):58–60

    Article  Google Scholar 

  138. Ju J, Li X, Kumar S, Jockusch S, Chien M, Tao C, Morozova I, Kalachikov S, Kirchdoerfer R, Russo JJ (2020) Nucleotide analogues as inhibitors of SARS-CoV polymerase. BioRxiv

    Google Scholar 

  139. Ramezankhani R, Solhi R, Memarnejadian A, Nami F, Hashemian SM, Tricot T, Vosough M, Verfaillie C (2020) Therapeutic modalities and novel approaches in regenerative medicine for COVID-19. Int J Antimicrob Agents 106208

    Google Scholar 

  140. Mickolajczyk KJ, Shelton PM, Grasso M, Cao X, Warrington SR, Aher A, Liu S, Kapoor TM (2020) Force-dependent stimulation of RNA unwinding by SARS-CoV-2 nsp13 helicase. BioRxiv

    Google Scholar 

  141. Jia Z, Yan L, Ren Z, Wu L, Wang J, Guo J, Zheng L, Ming Z, Zhang L, Lou Z (2019) Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucl Acids Res 47(12):6538–6550

    Article  Google Scholar 

  142. Hao W, Wojdyla JA, Zhao R, Han R, Das R, Zlatev I, Manoharan M, Wang M, Cui S (2017) Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathog 13(6):

    Article  Google Scholar 

  143. Russo M, Moccia S, Spagnuolo C, Tedesco I, Russo GL (2020) Roles of flavonoids against coronavirus infection. Chem-Biol Interact 109211

    Google Scholar 

  144. Shu T, Huang M, Di Wu YR, Zhang X, Han Y, Mu J, Wang R, Qiu Y, Zhang D-Y, Zhou X (2020) SARS-coronavirus-2 Nsp13 possesses NTPase and RNA helicase activities that can be inhibited by bismuth salts. Virologica Sinica 1

    Google Scholar 

  145. Yu M-S, Lee J, Lee JM, Kim Y, Chin Y-W, Jee J-G, Keum Y-S, Jeong Y-J (2012) Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg Med Chem Lett 22(12):4049–4054

    Article  Google Scholar 

  146. Keum Y-S, Jeong Y-J (2012) Development of chemical inhibitors of the SARS coronavirus: viral helicase as a potential target. Biochem Pharmacol 84(10):1351–1358

    Article  Google Scholar 

  147. Nittari G, Pallotta G, Amenta F, Tayebati SK (2020) Current pharmacological treatments for SARS-COV-2: a narrative review. Eur J Pharmacol 173328

    Google Scholar 

  148. Warrington R, Watson W, Kim HL, Antonetti FR (2011) An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol 7(S1):S1

    Article  Google Scholar 

  149. Christiaansen A, Varga SM, Spencer JV (2015) Viral manipulation of the host immune response. Curr Opin Immunol 36:54–60

    Article  Google Scholar 

  150. Magro G (2020) COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation inflammation cross-talking. Virus Res 198070

    Google Scholar 

  151. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W (2020) Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis

    Google Scholar 

  152. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L (2020) Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 323(16):1582–1589

    Article  Google Scholar 

  153. Khosravani H, Steinberg L, Incardona N, Quail P, Perri G-A (2020) Symptom management and end-of-life care of residents with COVID-19 in long-term care homes. Can Fam Physician 66(6):404–406

    Google Scholar 

  154. Lovell N, Maddocks M, Etkind SN, Taylor K, Carey I, Vora V, Marsh L, Higginson IJ, Prentice W, Edmonds P (2020) Characteristics, symptom management and outcomes of 101 patients with COVID-19 referred for hospital palliative care. J Pain Symptom Manage

    Google Scholar 

  155. Yang X, Liu Y, Liu Y, Yang Q, Wu X, Huang X, Liu H, Cai W, Ma G (2020) Medication therapy strategies for the coronavirus disease 2019 (COVID-19): recent progress and challenges. Expert Rev Clin Pharmacol 13(9):957–975

    Article  Google Scholar 

  156. Thickett DR, Armstrong L, Christie SJ, Millar AB (2001) Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med 164(9):1601–1605

    Article  Google Scholar 

  157. Ekström MP, Bornefalk-Hermansson A, Abernethy AP, Currow DC (2014) Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ 348

    Google Scholar 

  158. Speiser DE, Bachmann MF (2020) COVID-19: mechanisms of vaccination and immunity. Vaccines 8(3):404

    Article  Google Scholar 

  159. Lurie N, Saville M, Hatchett R, Halton J (2020) Developing Covid-19 vaccines at pandemic speed. N Engl J Med 382(21):1969–1973

    Article  Google Scholar 

  160. Haque A, Pant AB (2020) Efforts at COVID-19 vaccine development: challenges and successes. Vaccines 8(4):739

    Article  Google Scholar 

  161. Dong Y, Dai T, Wei Y, Zhang L, Zheng M, Zhou F (2020) A systematic review of SARS-CoV-2 vaccine candidates. Sig Transduction Targeted Therapy 5(1):1–14

    Google Scholar 

  162. Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC, Daniels AD, Jervey S (2020) Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Publications

    Google Scholar 

  163. WHO (2021) Draft landscape of COVID-19 candidate vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

  164. Saade F, Petrovsky N (2012) Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines 11(2):189–209

    Article  Google Scholar 

  165. Oroojalian F, Haghbin A, Baradaran B, Hemat N, Shahbazi M-A, Baghi HB, Mokhtarzadeh A, Hamblin MR (2020) Novel insights into the treatment of SARS-CoV-2 infection: an overview of current clinical trials. Int J Biol Macromol

    Google Scholar 

  166. Pardi N, Hogan MJ, Porter FW, Weissman D (2018) mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discovery 17(4):261

    Article  Google Scholar 

  167. NNanomedicine and the COVID-19 vaccines. Nat Nanotechnol 15(12):963–963

    Google Scholar 

  168. McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, Zhou J, Bouton CR, Rogers P, Polra K (2020) Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nature Commun 11(1):1–7

    Article  Google Scholar 

  169. Ghorbani A, Zare F, Sazegari S, Afsharifar A, Eskandari MH, Pormohammad A (2020) Development of a novel platform of virus-like particle (VLP)-based vaccine against COVID-19 by exposing epitopes: an immunoinformatics approach. New Microbes New Infect 38:

    Article  Google Scholar 

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    Authors and Affiliations

    1. Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

      Hossein Abolhassani, Ghazal Bashiri & Seyed Abbas Shojaosadati

    2. Protein Research Center, Shahid Beheshti University, Tehran, Iran

      Mahdi Montazeri & Hasan Kouchakzadeh

    3. Rahpouyan Fanavar Sadegh Company, Pardis Technology Park, 20th Km of Damavand Road, Tehran, Iran

      Seyed Ehsan Ranaei Siadat

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    1. Hossein Abolhassani
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    2. Ghazal Bashiri
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    4. Hasan Kouchakzadeh
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    5. Seyed Abbas Shojaosadati
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    Correspondence to Hasan Kouchakzadeh or Seyed Abbas Shojaosadati .

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    1. Protein Research Center, Shahid Beheshti University, Tehran, Iran

      Moones Rahmandoust

    2. Protein Research Center, Shahid Beheshti University, Tehran, Iran

      Seyed-Omid Ranaei-Siadat

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    Abolhassani, H., Bashiri, G., Montazeri, M., Kouchakzadeh, H., Shojaosadati, S.A., Siadat, S.E.R. (2021). Introduction to the Virus and Its Infection Stages. In: Rahmandoust, M., Ranaei-Siadat, SO. (eds) COVID-19. Springer, Singapore. https://doi.org/10.1007/978-981-16-3108-5_1

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