Certain biochemical aspects of coronavirus infection COVID-19

L. Kot, L.-A. Karpets, K. Sviridova, M. Chernikh, R. Prishlyak
Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv


An outbreak of coronavirus disease CoViD-19, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in a short period of time led to a global public health emergency worldwide. The difficult epidemiological situation associated with the rapid increase in the number of patients and the high mortality rate, as well as the need to overcome the
consequences of the pandemic as soon as possible, have become an important challenge for science. The special attention of scientists is focused on in-depth study of the pathogenetic mechanisms of coronavirus infection, which is important for the development of antiviral drugs and vaccines to combat CoViD-19. To penetrate the target cells the virus uses receptors,
expressed in various tissues of the organism, the main of which is angiotensin-converting enzyme 2 (ACE2). Virus replication is regulated by a lot of factors and causes abrupt morphological and physiological changes in cells. SARS-CoV-2 disrupts the regulation of inflammatory signaling pathways that generate a cytokine "storm", causes multisystem disorders and a life-threatening condition – acute respiratory distress syndrome. An important component of pathogenesis and clinical manifestations of CoViD-19 are hemostasis disorders, activation of thrombosis and thromboembolic complications. This review provides certain data regarding the structure of SARS-CoV-2, routes of infection, defense mechanisms against pathogen
invasion, features of the hemostasis system in coronavirus infection, intracellular signal transduction, and current strategies for the prevention and treatment of CoViD-19, which are aimed primarily at suppressing the replication of the virus, limiting its dissemination and reducing the immune response of organism in conditions of infection.


SARS-CoV-2, coronavirus infection, CoViD-19, signal regulation, therapeutic strategies

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Worldometer COVID-19 Data. – Electronic resource. – Available at https://www.worldometers.info/coronavirus/ (accessed June 03, 2021).

Naqvi TAA, Fatima K, Mohammad T, Fatima U, Indrakant K, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165878. doi: 10.1016/j.bbadis.2020.165878.

Parks J, Smith J. How to discover antiviral drugs quickly. New England J Med. 2020:1-4. doi: 10.1056/NEJMcibr2007042.

Zhang X, Li Sh, Niu Sh. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020;96(1137):403-407.

Watanabe Ya, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science. 2020;369(6501):330-333.

Zaloilo I, Rud Y, Zaloilo О, Buchatskyi L. Coronavirus viroporins: structure and function. Ukr Biochem J. 2021;93(1):5-17.

Alsobaie S. Understanding the molecular biology of SARS-CoV-2 and the COVID-19 pandemic: a review. Infect Drug Resist. 2021;14:2259-2268.

Sun C-b, Wang Y-ye, Liu G-hao, Liu Z. Role of the eye in transmitting human coronavirus: what we know and what we do not know. Front Public Health. 2020;8:155.

Gallo O, Locatello LG, Mazzoni A, et al. The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol. 2021;14,305-316.

Kim YI, Kim SG, Kim SM. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe. 2020;27:704-709.

Lutz C, Maher L, Lee C, et al. COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice. Hum Genomics 2020:20. https://doi.org/10.1186/s40246-020-00272-6.

Alenina N, Bader M. ACE2 in brain physiology and pathophysiology: evidence from transgenic animal models. Neurochem Res. 2019;44(6):1323-1329.

Lew RA, Warner FJ, Hanchapola I, Yarski MA, Ramchand J, Burrell LM, Smith AI. Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor. Exp Physiol. 2008;93(5):685-93.

Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan COVID-19. doi: 202010.1101/2020.01.26.919985

Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: angiotensinconverting enzyme 2 (ACE2) expression and tissue susceptibility to SARSCoV-2 infection. Eur J Clin Microbiol Infect Dis. 2021;40:905-919.

Huang C, Wang Y, Li X, Ren L, Zhao J, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020. doi: 10.1016/S0140-6736(20)30183-5.

Guan W, Ni Z, Hu Y, Liang W, Ou C, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv. 2020. doi:10.1101/2020.02.06.20020974.

Wadman M. How does coronavirus kill? clinicians trace a ferocious rampage through the body, from brain to toes. Science. 2020;2:abc3208. doi:10.1126/science.abc3208.

Soldo J, Heni M, Konigsrainer A, Haring HU, Birkenfeld AL, Peter A. Increased hepatic ACE2 expression in NAFL and diabetes – a risk for COVID-19 patients? Diabetes Care. 2020;43(10):e134-6. doi: 10.2337/dc20-1458.

Shi S, Qin M, Shen B, Cai Y, Liu T, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiology. 2020;25:e200950. doi: 10.1001/jamacardio.2020.0950.

Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-

Cholankeril G, Podboy A, Aivaliotis VI, Tarlow B, Pham EA, Spencer SP, Kim D, Hsing A, Ahmed A. High prevalence of concurrent gastrointestinal manifestations in patients with severe acute respiratory syndrome coronavirus 2: early experience from California. Gastroenterology. 2020;159(2):775-777.

Pan L, Mu M, Yang P, Sun Y, Wang R, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in hubei, china: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol. 2020;115(5):766-773.

Su H, Yang M, Wan C, Yi LX, Tang F, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney International. 2020;98:219-227.

Lucena TMC, Santos AFS, Lima BR, Borborema MEA, Silva JA. Mechanism of inflammatory response in associated comorbidities in COVID-19 Diabetes Metab Syndr. 2020;14(4):597-600.

Leng PZ, Zhu R, Hou W, Feng Y, Yang Y, et al. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19. Aging Dis. 2020;11(2):216-228.

Wang K, Chen W, Zhang Z, et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Sig Transduct Target Ther 2020;5:283.

Shilts J, Crozier TWM, Greenwood EJD, et al. No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor. Sci Rep. 2021;11:413.

Radzikowska U, Ding M, TanG, Zhakparov D, Peng Y, et al. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, 1. Worldometer COVID-19 Data. – Electronic resource. – Available at https://www.worldometers.info/coronavirus/ (accessed June 03, 2021).

obesity, hypertension, and COVID-19 risk factors. Allergy. 2020;75(11):2829-2845.

Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020:eabd2985. doi: 10.1126/science.abd2985.

Mayi BS, Leibowitz JA, Woods AT, Ammon KA, Liu AE, Raja A. The role of Neuropilin-1 in COVID-19. PLoS Pathog. 2021;17(1):e1009153. doi: 10.1371/journal.ppat.1009153.

Sigrist CJA, Bridge A, Mercier PL. A potential role for integrins in host cell entry by SARS-CoV-2. Antiviral Res. 2020;177:104759.

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(2):271-280.e8.

Padmanabhan P, Desikan R, Dixit NM. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection. PLoS Comput Biol. 2020;16(12):e1008461. doi: 10.1371/journal.pcbi.1008461.

Nakagawa K, Lokugamage KG, Makino S. Viral and cellular mRNA translation in coronavirus-infected cells. Adv Virus Res. 2016;96:165-192.

Zhao M-M, Yang W-L, Yang F-Y, Zhang L, et al. 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. Signal Transduct Target Ther. 2021;6:134.

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

Shamsi A, Mohammad T, Anwar S, AlAjmi MF, Hussain A, Rehman MT, Islam A, Hassan MI. Glecaprevir and Maraviroc are highaffinity inhibitors of SARS-CoV-2 main protease: possible implication in COVID-19 therapy. Biosci Rep. 2020:40. doi: 10.1042/BSR20201256.

Li G, Fan Y, Lai Y, Han T, Li Z, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424-432.

Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008.

Vijay K. Toll-like receptors in immunity and inflammatory diseases: past, present, and future. Int Immunopharmacol. 2018;59:391-412.

Subbarao K, Mahanty S. Respiratory virus infections: understanding COVID-19. Immunity. 2020;52(6):905-909.

Moens L, Meyts I. Recent human genetic errors of innate immunity leading to increased susceptibility to infection. Curr Opin Immunol. 2020;62:79-90.

Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and pyroptosis as therapeutic targets for COVID-19. J Immunol 2020;205(2):307-12.

Ye Q, Wang B, Mao J. et al. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020. pii: S0163-4453(20)30165-1.

Chen Z, Wherry JE. T cell responses in patients with COVID-19. Nat Rev Immunol 2020;20:529-536.

Amiral J, Vissac AM, Seghatchian J. CoViD-19, induced activation of hemostasis, and immune reactions: Can an auto-immune reaction contribute to the delayed severe complications observed in some patients? Transfus Apher Sci. 2020;59(3):102804.

Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-147.

Fogarty H, Townsend L, Ni Cheallaigh C, Bergin C, et al. More on COVID-19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189(6):1060-1061.

Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection 2020. Clin Chem Lab Med. 2020;25;58(7):1131-1134.

García-Ortega A, de la Rosa D, Oscullo G, Castillo-Villegas D, López-Reyes R, Martínez-García MÁ. Coagulation disorders and thromboembolic disease in COVID-19: review of current evidence in search of a better approach. J Thorac Dis. 2021;13(2):1239-1255.

Battagello DS, Dragunas G, Klein MO, Ayub ALP, Velloso FJ, Correa RG. Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission. Clin Sci (Lond) 2020;134(16):2137-2160.

Zhao C, Zhao W. NLRP3 inflammasome-a key player in antiviral responses. Front Immunol. 2020;11:211. https://doi.org/10.3389/fimmu.2020.00211.

Hemmat N, Asadzadeh Z, Ahangar NK, et al. The roles of signaling pathways in SARS-CoV-2 infection; lessons learned from SARS-CoV and MERS-CoV. Arch Virol 2021;166:675-696.

Lee SJ, Channappanavar R, Kanneganti T-D. Coronaviruses: innate immunity, inflammasome activation, inflammatory cell death, and cytokines. Trends Immunol. 2020;41(12):1083-1099.

Venkataraman T, Frieman MB.The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis. Antivir Res 2017;143:142-150.

Luo W, Li Y-X, Jiang L-J, et al. Targeting JAK-STAT signaling to control cytokine release syndrome in COVID-19. Trends Pharmacol Sci. 2020;41:531-543.

Chen LYC, Biggs CM, Jamal S, Stukas S, Wellington CL, Sekhon MS, Soluble interleukin-6 receptor in the COVID-19 cytokine storm syndrome. Cell Reports Medicine. 2021;2(5):100269.

Bouwman W, Verhaegh W, Holtzer L, et al. Measurement of cellular immune response to viral infection and vaccination. Front Immunol. 2020;11:1-13.

Rojas P, Sarmiento M. JAK/STAT pathway inhibition may be a promising therapy for COVID-19-related hyperinflammation in hematologic patients. Acta Haematol. 2020:1-5.

Annweiler C, Cao Z, Wu Y, Faucon E, Mouhat S, Kovacic H, Sabatier JM. Counter-regulatory 'renin-angiotensin' system-based candidate drugs to treat COVID-19 diseases in SARS-CoV-2-infected patients. Infect Disord Drug Targets. 2020;20(4):407-408.

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(2):271-280.

Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381-5.

Zhang J, Xie B, Hashimoto K. Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behav Immun. 2020;87:59-73.

Cruz FF, Rocco PRM. The potential of mesenchymal stem cell therapy for chronic lung disease. Expert Rev Respirat Med. 2020;14:31-39. 66. Duan K, Liu B, Li C, Zhang H, Yu T, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490-9496.

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033-2040.

Wouters OJ, Shadlen KC, Salcher-Konrad M, Pollard AJ, Larson HJ, Teerawattananon Y, Jit M. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. Lancet. 2021;397:1023-34.

COVID-19 vaccine tracker – Electronic resource. – Available at https://vac- lshtm.shinyapps.io/ncov_vaccine_landscape/ (Last updated on 19 June 2021).

Kumar AU, Kadiresen K, Gan WC, Ling APK Current updates and research on plant-based vaccines for coronavirus disease 2019. Clin Exp Vaccine Res. 2021;10(1):13-23.

Received: 03.09.2021

Revised: 05.10.2021

Signed for publishing: 05.10.2021

DOI: http://dx.doi.org/10.17721/1728_2748.2021.86.17-22


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