DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20203478

Model of trigger mechanisms of SARS CoV-2 infections

Nestor Cahui Galarza, Maria De Los Angeles Monge Condori

Abstract


Coronavirus disease-2019, is a pandemic that is causing great loss of life and economy. Knowledge of the pathogenesis of the disease is required for the control and treatment of clinical manifestations. The aim of this review is to analyses the information on the molecular mechanisms that trigger the alterations caused by SARS-CoV-2 from published articles related to COVID-19. The onset of the COVID-19 virus infection in humans occurs when the SARS-CoV-2 S protein reaches cells containing ACE2 receptors, being mainly the upper respiratory tract, followed by the oral cavity, and in lesser frequency through the conjunctiva. Inflammation and thrombus formation in symptomatic patients have been the major cause of SARS-CoV-2 aggravation, this occurs largely due to the imbalance of regulation by diminishing ACE2 receptors, which serves to activate the regulatory axis Ang-II→ACE2→Ang-(1-7)→MAS receptor, which counteracts the negative actions caused by Ang-II. The ACE2 is also the main receiver for the SARS-CoV-2 so that it can trigger the virulence processes in the host.


Keywords


Coagulation, COVID-19, Pathogenesis, Pyroptosis

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References


Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China. The Lancet 2020;395:689-97.

Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19). Int J Antimicrobial Agents 2020;55:105924.

Xu H. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Science 2020;12:1-5.

Nikitina E, Larionova I, Choinzonov E, Kzhyshkowska J. Monocytes and macrophages as viral targets and reservoirs. Int J Molecular Sci. 2018 Sep;19(9):2821.

Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochemical and Biophysical Research Communications 2020;525;135-40.

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

Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Ann Rev Virol. 2016 Sep 29;3:237-61.

Millet JK, Whittaker GR. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015 Apr 16;202:120-34.

Holmes KV. SARS coronavirus: a new challenge for prevention and therapy. J Clin Investig. 2003 Jun 1;111(11):1605-9.

Bosch BJ, Bartelink W, Rottier PJ. Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide. J Virol. 2008 Sep 1;82(17):8887-90.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 Mar 13;367(6483):1260-3.

Luan J, Lu Y, Jin X, Zhang L. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochemical and biophysical research communications. 2020 Mar 19.

Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012 Jun;4(6):1011-33.

Pallesen J, Wang N, Corbett KS, Wrapp D, Kirchdoerfer RN, Turner HL, et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc National Academy Scie. 2017 Aug 29;114(35):E7348-57.

Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S, Qi F, et al. Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. bioRxiv. 2020 Jan 1.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Mar 5.

Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell research. 2017 Jan;27(1):119-29.

Walls AC, Tortorici MA, Snijder J, Xiong X, Bosch BJ, Rey FA, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proce Nat Acad Scie. 2017 Oct 17;114(42):11157-62.

Epand RM. Fusion peptides and the mechanism of viral fusion. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2003 Jul 11;1614(1):116-21.

Lu L, Liu Q, Zhu Y, Chan KH, Qin L, Li Y, et al. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nature communications. 2014 Jan 28;5(1):1-2.

Abiodun OA, Ola MS. Role of brain renin angiotensin system in neurodegeneration: An update. Saudi J Biol Scie. 2020 Mar 1;27(3):905-12.

Natarajan A, Van Anthony MV, Jose PA. The Renin-Angiotensin System. Nephrol Fluid/electrolyte Physiol. 2019:165-88.

Aguilera G. Stress, Angiotensin, and Cognate Receptors. Stress. vol. 2 Elsevier Inc., 2017.

Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO molecular medicine. 2010 Jul;2(7):247-57.

Turner AJ, Hooper NM. Angiotensin-converting enzyme 2. Handbook of Proteolytic Enzymes: 2nd ed, 2004: 349-352.

Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin-converting enzyme–related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research. 2000 Sep 1;87(5):e1-9.

Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GV, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol: J Patholog Society Great Britain and Ireland. 2004 Jun;203(2):631-7.

Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Inter Med. 2020 Apr 20.

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005 Jul;436(7047):112-6.

Kuba K, Imai Y, Penninger JM. Angiotensin-converting enzyme 2 in lung diseases. Current Opinion Pharmacol. 2006 Jun 1;6(3):271-6.

Li G, He X, Zhang L, Ran Q, Wang J, Xiong A, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmunity. 2020 Apr 13:102463.

Isaksson R, Casselbrant A, Elebring E, Hallberg M, Larhed M, Fändriks L. Direct stimulation of angiotensin II type 2 receptor reduces nitric oxide production in lipopolysaccharide treated mouse macrophages. Eur J Pharmacol. 2020 Feb 5;868:172855.

Queiroz-Junior CM, Santos AC, Galvão I, Souto GR, Mesquita RA, Sá MA, et al. The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor axis as a key player in alveolar bone remodeling. Bone. 2019 Nov 1;128:115041.

Marshall RP, McANULTY RJ, Laurent GJ. Angiotensin II is mitogenic for human lung fibroblasts via activation of the type 1 receptor. Am J Respirat Critic Med. 2000 Jun 1;161(6):1999-2004.

Sampaio WO, dos Santos RA. Endothelium and the Renin-Angiotensin System. InEndothelium and Cardiovascular Diseases 2018 Jan 1:203-11

Galindo M, Santiago B, Palao G, Gutierrez-Cañas I, Ramirez JC, Pablos JL. Coexpression of AT1 and AT2 receptors by human fibroblasts is associated with resistance to angiotensin II. Peptides. 2005 Sep 1;26(9):1647-53.

Walters PE, Gaspari TA, Widdop RE. Angiotensin-(1–7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension. 2005 May 1;45(5):960-6.

Dias-Peixoto MF, Santos RA, Gomes ER, Alves MN, Almeida PW, Greco L, et al. Molecular mechanisms involved in the angiotensin-(1-7)/Mas signaling pathway in cardiomyocytes. Hypertension. 2008 Sep 1;52(3):542-8.

Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infectious Disea. 2004 Nov 15;39(10):1531-5.

Lei C, Su B, Dong H, Bellavia A, Di Fenza R, Fakhr BS, et al. Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2). Med Rxiv. 2020 Jan 1.

Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circulation Res. 2001 Apr 27;88(8):756-62.

Gambaryan S, Geiger J, Schwarz UR, Butt E, Begonja A, Obergfell A, et al. Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase. Blood. 2004 Apr 1;103(7):2593-600.

Fraga-Silva RA, Da Silva DG, Montecucco F, Mach F, Stergiopulos N, da Silva RF, et al. The angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas receptor axis: a potential target for treating thrombotic diseases. Thrombosis Haemostasis. 2012;108(12):1089-96.

Yang Y. The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. J Autoimmun. 2020;109:102434.

Yu CJ. Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus. FEBS Letters 2004;565;111-6.

Khan S, Ng ML, Tan YJ. Expression of the severe acute respiratory syndrome coronavirus 3a protein and the assembly of coronavirus-like particles in the Baculovirus expression system. Methods Molecular Biol. 2007;379:35-50.

Zhang X, Xu A, Lv J, Zhang Q, Ran Y, Wei C, et al. Development of small molecule inhibitors targeting NLRP3 inflammasome pathway for inflammatory diseases. Eur J Medicinal Chemistry. 2020 Jan 1;185:111822.

Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, et al. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005 Jun 15;79(12):7819-26.

Yilla M, Harcourt BH, Hickman CJ, McGrew M, Tamin A, Goldsmith CS, et al. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005 Jan 1;107(1):93-101.

Guan CS, Lv ZB, Yan S, Du YN, Chen H, Wei LG, et al. Imaging features of coronavirus disease 2019 (COVID-19): evaluation on thin-section CT. Academic Radiol. 2020 Mar 20.