Immune mechanisms of SARS-CoV-2 and potential drugs in the prevention and treatment of COVID-19
https://doi.org/10.18093/0869-0189-2020-30-5-700-708
Abstract
The lack of specific vaccines against SARS-CoV-2, as well as chemotherapy, significantly affected the spread of infection and the number of adverse outcomes of COVID-19. With the discovery of the pathogenesis of coronavirus infection, especially immune mechanisms, the important role of the innate immunity system in interacting with the virus is obvious. The presence of comorbid conditions, as well as the aging of the body, lead to disturbances in the immune response mechanism, low interferon induction, depletion of CD8+ -lymphocytes and natural killers and suppression of the effectiveness of both innate and adaptive immunity. The review discusses various mechanisms of antiviral activity associated with the induction of interferon (IFN) production, the use of direct IFN therapy, the use of antiviral drugs, and immunotropic therapy (synthetic immunomodulators), as promising in the prevention and treatment of COVID-19.
About the Authors
M. P. Kostinov
I.I.Mechnikov Research Institute of Vaccines and Sera; I.M.Sechenov First Moscow State Medical University (Sechenov University), Healthcare Ministry of Russia
Russian Federation
Russian Federation
Mikhail P. Kostinov – Doctor of Medicine, Professor, Head of Vaccine Prophylaxis and Immunotherapy of Allergic Diseases Laboratory, I.I.Mechnikov Research Institute of Vaccines and Sera Professor; Professor at the Department of Epidemiology and Modern Vaccination Technologies, I.M.Sechenov First Moscow State Medical University (Sechenov University), Healthcare Ministry of Russia
Malуy Kazennуy per. 5A, Moscow, 105064
ul. Trubetskaya 8, build. 2, Moscow, 119991
tel.: (495) 917-41-49
E. V. Markelova
Pacific State Medical University, Healthcare Ministry of Russia
Russian Federation
Russian Federation
Elena V. Markelova – Doctor of Medicine, Professor, Head of the Department of Normal and Pathological Physiology
Ostryakova pr. 2, Vladivostok, 690002
tel.: (423) 245-07-00
O. A. Svitich
I.I.Mechnikov Research Institute of Vaccines and Sera
Russian Federation
Russian Federation
Oksana A. Svitich – Doctor of Medicine, Corresponding Member of Russian Academy of Sciences, Director, Head of Molecular Immunology Laboratory
Malуy Kazennуy per. 5A, Moscow, 105064
tel.: (495) 917-49-00
V. B. Polishchuk
I.I.Mechnikov Research Institute of Vaccines and Sera
Russian Federation
Russian Federation
Valentina B. Polishchuk – Candidate of Medicine, Lead Researcher of Vaccine Prophylaxis and Immunotherapy of Allergic Diseases Laboratory
Malуy Kazennуy per. 5A, Moscow, 105064
tel.: (495) 917-41-49
References
1. Yaqinuddin A., Kashir J. Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents. Med. Hypotheses. 2020; 140: 109777. DOI: 10.1016/j.mehy.2020.109777.
2. Kai H., Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens. Res. 2020; 43 (7): 648–654. DOI: 10.1038/s41440-020-0455-8.
3. Arias-Reyes C., Zubieta-DeUrioste N., Poma-Machicao L. et al. Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? Respir. Physiol. Neurobiol. 2020; 277: 103443. DOI: 10.1016/j.resp.2020.103443.
4. Tay M.Z., Poh C.M., Rénia L. et al. The trinity of COVID19: immunity, inflammation and intervention. Nat. Rev. Immunol. 2020; 20 (6): 363–374. DOI: 10.1038/s41577-0200311-8.
5. Kato H., Takeuchi O., Sato S. et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006; 441 (7089): 101–105. DOI: 10.1038/nature04734.
6. Cao W., Li T. COVID-19: towards understanding of pathogenesis. Cell Res. 2020; 30 (5): 367–369. DOI: 10.1038/s41422-020-0327-4.
7. de Lucena T.M.C., da Silva Santos A.F., de Lima B.R. et al. Mechanism of inflammatory response in associated comorbidities in COVID-19. Diabetes Metab. Syndr. 2020; 14 (4): 597–600. DOI: 10.1016/j.dsx.2020.05.025.
8. Mihm S. COVID-19: Possible impact of the genetic background in IFNL genes on disease outcomes. J. Innate Immun. 2020; 12 (3): 273–274. DOI: 10.1159/000508076.
9. Taghizadeh-Hesary F., Akbari H. The powerful immune system against powerful COVID-19: A hypothesis. Med. Hypotheses. 2020; 140: 109762. DOI: 10.1016/j.mehy.2020.109762.
10. Andreakos E., Tsiodras S. COVID-19: lambda interferon against viral load and hyperinflammation. EMBO Mol. Med. 2020; 12 (6): e12465. DOI: 10.15252/emmm.202012465.
11. Jin Y., Yang H., Ji W. et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020; 12 (4): 372. DOI: 10.3390/v12040372.
12. Vaninov N. In the eye of the COVID-19 cytokine storm. Nat. Rev. Immunol. 2020; 20 (5): 277. DOI: 10.1038/s41577020-0305-6.
13. Joly B.S., Siguret V., Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med. 2020; 46 (8): 16031606. DOI: 10.1007/s00134-020-06088-1.
14. Sokolova T.M., Poloskov V.V., Shuvalov A.N. [Grippol and Vaxigrip vaccines – activators of gene expression of the innate immunity system in acute monocytic leukemia cells TNP-1]. Evraziyskiy soyuz uchenykh. 2016; 5 (26): 61–63. Available at: https://cyberleninka.ru/article/n/vaktsiny-grippol-i-vaksigrip-aktivatory-ekspressii-genov-sistemy-vrozhdennogo-immuniteta-v-kletkah-ostroy-monotsitarnoy-leykemii-tnr1/viewer (in Russian).
15. Sokolova T.M., Shuvalov A.N., Poloskov V.V. et al. [Grippol, Vaxigrip and Influvac vaccines – inductors of innate and adaptive immunity factor genes in human blood cells]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2014; (5): 37–43 (in Russian).
16. Sokolova T.M., Shuvalov A.N., Poloskov V.V. et al. [Simulation of signaling receptors gene expression and induction of synthesis of cytokines in human blood cells by drug Ribonucleat sodium and its combination with inactivated influenza vaccines]. Molekulyarnaya meditsina. 2015; (1): 12–17 (in Russian).
17. Kostinov M.P., Akhmatova N.K., Khromova E.A. et al. The impact of adjuvanted and nonadjuvanted influenza vaccines on the innate and adaptive immunity effectors. In: Saxena S.K., ed. Influenza – therapeutics and challenges. Chapter 5. London: IntechOpen; 2018: 83–109. DOI: 10.5772/intechopen.77006.
18. Khromova E.A., Akhmatova E.A., Skhodova S.A. et al. [Effect of influenza vaccines on subpopulations of blood dendritic cells]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2016; (5): 23–28. DOI: 10.36233/03729311-2016-5-23-28 (in Russian).
19. Alexia C., Cren M., Louis-Plence P. et al. Polyoxidonium® activates cytotoxic lymphocyte responses through dendritic cell maturation: Clinical effects in breast cancer. Front. Immunol. 2019; 10: 2693. DOI: 10.3389/fimmu.2019.02693.
20. Talaev V.Yu., Matveichev A.V., Zaichenko I.E. et al. [Polyoxidonium ® vaccine adjuvant enhances the immune response to low dose of influenza antigens]. In: [Scientific support of anti-epidemic protection of the population: urgent problems and solutions: Collected scientific papers]. N. Novgorod: Remedium Privolzh’e; 2019: 363–365 (in Russian).
21. Mavzyutova G.A., Mukhamadieva L.R., Fazlyeva R.M. et al. [Rational immunotherapy in the combination treatment of community-acquired pneumonia]. Meditsinskiy sovet. 2015; (16): 68–73 (in Russian).
22. Illek Ya.Yu., Galanina A.V., Zaytseva G.A. [The effectiveness of polyoxidonium in severe pneumonia in young children]. Terra Medica Nova. 2005; (3): 12–14 (in Russian).
23. Averkiev V.L., Tarasenko V.S., Latysheva T.V., Averkieva L.V. [Correction of immunological disorders in patients with pancreatic necrosis]. Immunologiya. 2002; 23 (6): 359–363 (in Russian).
24. Gavrilyuk V.P., Konoplya A.I. [Effect of immunomodulators on the clinical course of appendicular peritonitis in children]. Detskaya khirurgiya. 2012; (4): 36–38 (in Russian).
25. Gordinskaya N.A., Pylaeva S.I., Sidorkin V.G., Aminev V.A. [Effect of Polyoxidonium on the level of intoxication in burn patients]. Immunologiya. 2002; (6): 363–365 (in Russian).
26. [Vyšetrovací algoritmus a medikamentózna liečba pacientov nad 65 rokov, pacientov so závažným priebehom a polymorbídnych pacientov počas hospitalizácie na infekčnom oddelení]. Available at: https://korona.gov.sk/wp-content/uploads/2020/04/COVID-19-hospitalizovan%C3%ADpacientiv-nad-65-rokov-lie%C4%8Dba-infekcne-oddelenia-verzia-2.0.pdf (in Slovak). / [Examination algorithm and drug treatment of patients over 65 years of age, patients with severe course and polymorbid patients during hospitalization in the infection department]. Available at: https://korona.gov.sk/wp-content/uploads/2020/04/COVID-19-hospitalizovan%C3%AD-pacientiv-nad-65-rokov-lie%C4%8Dba-infekcneoddelenia-verzia-2.0.pdf (in Slovak).
27. Luss L.V., MartynovRadushinskiy A.A. [Role and place of immunomodulation therapy in the treatment of infectious inflammatory diseases in combination with secondary immune deficiency]. Medicinskiy sovet. 2013; (11): 78–81 (in Russian).
28. Masternak Yu.A., Luss L.V. [The effect of Polyoxidonium on the parameters of the immune status of elderly people]. Immunologiya. 2002; (6): 343–346 (in Russian).
29. Parahonskiy A.P. [Clinical and immunological characteristics of immune deficiency and its correction in the elderly patients]. Sovremennye naukoemkie tekhnologii. 2008; (7): 89–90 (in Russian).
30. Serbin A.S., Fomichev E.V., Afanas’eva O.Yu., Aleshanov K.A. [Immune status of elderly patients with odontogenic phlegmon of maxillofacial region along with taking immuno-modulary therapy]. Medicinskiy alfavit. 2016; 2 (9 (272)): 65–67 (in Russian).
31. Nesterova I.V. [Interferon alpha preparations in clinical practice: when and how]. Lechashchiy vrach. 2017; (9): 66–76 (in Russian).
32. Nesterova I.V. [Congenital and acquired interferonopathies: differentiated approaches to the interferon-corrective therapy]. Detskie infektsii. 2017; 2 (16): 50–53. DOI: 10.22627/2072-8107-2017-16-2-50-53 (in Russian).
33. Al-Herz W, Bousfiha A, Casanova J.L. et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front. Immunol. 2014; 5: 162. DOI: 10.3389/fimmu.2014.00162.
34. Chuchalin A.G., Aleksandrovskiy Ju.A., Ametova A.S. et al., eds. [Federal guidelines for the use of drugs (formulary system). Moscow: Ekho; 2015. Is. XVI (in Russian).
35. Kostinov. M.P., ed. [Immunocorrection in Pediatrics: A Practical Guide for Physicians]. Moscow: Meditsina dlya vsekh; 1997 (in Russian).
36. Meshcheryakova A.K., Kostinov M.P., Magarshak O.O. et. al. [Local immunity levels in pregnant women with acute respiratory infection against the background of interferon therapy]. Voprosy ginekologii, akusherstva i perinatologii. 2014; 13 (2): 44–48 (in Russian).
37. Meshcheryakova A.K., Kostinov M.P., Magarshak O.O. et al. [The influence of gel-like recombinant interferon α-2b on the clinical course of acute respiratory infection and the state of mucosal immunity in the pregnant women]. Vestnik otorinolaringologii. 2014; (6): 50–53. DOI: 10.17116/otorino2014-650-53 (in Russian).
38. Kostinov M.P., Lukachev I.V., Meshcheryakova A.K. et al. [Induction of effectors of innate and adaptive immunity in the process of therapy of topic form of recombinant interferon-α2b during respiratory infections in pregnant]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2017; (2): 38–45. DOI: 10.36233/0372-9311-2017-2-38-45 (in Russian).
39. Kostinov M.P., Lukachev I.V., Meshcheryakova A.K. et al. [Preventing complications in pregnant women with mild and moderate severity of acute respiratory infections]. Epidemiologiya i vaktsinoprofilaktika. 2018; 17 (1): 62–73 (in Russian).
40. Krasnov V.V. [Influenza and acute respiratory infections: the use of recombinant interferon for treatment and prevention in children]. Praktika pediatra. 2019; (1): 24–29 (in Russian).
41. Sallard E., Lescure F-X., Yazdanpranh Y. et al. Type 1 interferons as a potential treatment against COVID-19. Antiviral Res. 2020; 178: 104791. DOI: 10.1016/j.antiviral.2020.104791.
42. Prokunina-Olsson L., Alphonse N., Dickenson R.E. et al. COVID-19 and emerging viral infections: The case for interferon lambda. J. Exp. Med. 2020; 217 (5): e20200653. DOI: 10.1084/jem.20200653.
43. Sokolova T.M., Uryvaev L.V., Tazulahova Je.B. et al. [Individual changes of gene expression in the interferon system in human blood cells due to amixin and cycloferon]. Voprosy virusologii. 2005; 50 (2): 32–36 (in Russian).
44. Bazhanova E.D. [Cycloferon: mechanism of action, functions and application]. Eksperimental’naya i klinicheskaya farmakologiya. 2012; 75 (7): 40–44 (in Russian).
45. Shul’dyakov A.A., Lyapina E.P., Soboleva L.A. et al. [The use of interferon inducers in an infectious disease clinic]. Antibiotiki i khimioterapiya. 2018; 63 (3–4): 28–36 (in Russian).
46. Tereshin V.A., Sotskaya Ya.A., Kruglova O.V. [Efficacy of cycloferon in the treatment and prevention of influenza and acute respiratory infections in children and teenagers]. Rossiyskiy vestnik perinatologii i pediatrii. 2014; 59 (2): 103108 (in Russian).
47. Yin M., Zhang Y., Li H. Advances in research on immunoregulation of macrophages by plant polysaccharides. Front. Immunol. 2019; 10: 145. DOI: 10.3389/fimmu.2019.00145.
48. Shim E.H., Choung S.Y. Inhibitory effects of Solanum tuberosum L. var. vitelotte extract on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice. J. Pharm. Pharmacol. 2014; 66 (9): 1306–1316. DOI: 10.1111/jphp.12254.
49. Kang M.A., Choung S.Y. Solanum tuberosum L. cv Hongyoung extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Mol. Med. Rep. 2016; 14 (4): 3093–3103. DOI: 10.3892/mmr.2016.5595.
50. Ashakher T., Krokhin A., Kuznetsova I. et al. [Effect of the preparation Ingavirin® (imidazolyl ethanamide pentandioic acid) on the interferon status of cells under conditions of viral infection]. Epidemiologiya i infektsionnye bolezni. 2016; 21 (4): 196–205. DOI: 10.18821/1560-9529-201621-4-196-205 (in Russian).
51. Farber I.M., Geppe N.A., Reykhart D.V. et al. [Therapy for influenza and acute respiratory viral infection in young and middle-aged schoolchildren: Effect of Ingavirin ® on intoxication, fever, and catarrhal syndromes]. Rossiyskiy vestnik perinatologii i pediatrii. 2016; 61 (2): 115–120 (in Russian).
52. Leneva I.A., Russell R.J., Boriskin Y.S., Hay A.J. Characteristics of Arbidol-resistant mutants of influenza virus: Implications for the mechanism of anti-influenza action of Arbidol. Antiviral Res. 2009; 81 (2): 132–140. DOI: 10.1016/j.antiviral.2008.10.009.
53. Boriskin Y., Leneva I., Pecheur E., Polyak S.J. Arbidol: a broad-spectrum antiviral compound that bloks viral fusion. Curr. Med. Chem. 2008; 15 (10): 997–1005. DOI: 10.2174/092986708784049658.
54. Delogu I., Pastorino B., Baronti C. et al. In vitro antiviral activity of Аrbidol against Chikungunya virus and characteristics of a selected resistant mutant. Antiviral Res. 2011; 90 (3): 99–107. DOI: 10.1016/j.antiviral.2011.03.182.
55. Brooks M.J., Burtseva E.I., Ellery P.J. et al. Antiviral activity of Аrbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions. J. Med. Virol. 2012; 84 (1): 170–181. DOI: 10.1002/jmv.22234.
56. Burtseva E.I., Shevchenko E.S., Belyakova N.V. et al. [Monitoring of the sensitivity of epidemic influenza virus strains isolated in Russia to etiotropic chemical agents]. Voprosy virusologii. 2009; (2): 24–28 (in Russian).
57. Vartanyan R.V., Cheshik S.G., Kolobukhina L.V., Malyshev N.A. [Treatment of acute respiratory viral infections and influenza in preschool children by Kagoсel® ]. Meditsinskie novosti. 2015; 12 (255): 29–31 (in Russian).
58. Zuykova I.N., Shul’zhenko A.E., Shchubelko R.V. [Interferon inducer Kagocel ® in the complex treatment of herpes virus diseases]. Farmateka. 2014; 3 (276): 23–29 (in Russian).
59. Ma C., Sacco M.D., Hurst B. et al. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. 2020; 30 (8): 678–692. DOI: 10.1038/s41422-020-0356-z.
60. Scott I.C., Hider S.L., Scott D.L. Thromboembolism with Janus Kinase (JAK) inhibitors for rheumatoid arthritis: How real is the risk? Drug Saf. 2018; 41 (7): 645–653. DOI: 10.1007/s40264-018-0651-5.
61. Mehta P., Ciurtin C., Scully M. et al. JAK inhibitors in COVID-19: the need for vigilance regarding increased inherent thrombotic risk. Eur. Respir. J. 2020; 56 (3): 2001919. DOI: 10.1183/13993003.01919-2020.
62. Ulrich H., Pillat M.M. CD147 as a target for COVID-19 treatment: Suggested effects of Azithromycin and stem cell engagement. Stem Cell Rev. Rep. 2020; 16 (3): 434–440. DOI: 10.1007/s12015-020-09976-7.
63. Liu C., Zhu D. Cyclophilin A and CD147: novel therapeutic targets for the treatment of COVID-19. Med. Drug Discov. 2020; 7: 100056. DOI: 10.1016/j.medidd.2020.100056.
Review
For citations:
Kostinov M.P., Markelova E.V., Svitich O.A., Polishchuk V.B. Immune mechanisms of SARS-CoV-2 and potential drugs in the prevention and treatment of COVID-19. PULMONOLOGIYA. 2020;30(5):700-708. https://doi.org/10.18093/0869-0189-2020-30-5-700-708
Views:
1646
Email this article 