Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.

Autor: Akbasheva OE; Siberian State Medical University, 634050 Tomsk, Russia., Spirina LV; Siberian State Medical University, 634050 Tomsk, Russia.; Cancer Research Institute, Tomsk National Research Medical Center, 634009 Tomsk, Russia., Dyakov DA; Siberian State Medical University, 634050 Tomsk, Russia., Masunova NV; Siberian State Medical University, 634050 Tomsk, Russia.
Jazyk: angličtina
Zdroj: Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry [Biochem Mosc Suppl B Biomed Chem] 2022; Vol. 16 (4), pp. 271-291. Date of Electronic Publication: 2022 Nov 16.
DOI: 10.1134/S1990750822040035
Abstrakt: The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α 1 -proteinase inhibitor (α 1 -PI, α 1 -antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α 1 -PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α 1 -antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α 1 -PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α 1 -PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone-angiotensin-renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α 1 -PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α 1 -PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α 1 -PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.
Competing Interests: The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
(© Pleiades Publishing, Ltd. 2022, ISSN 1990-7508, Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 2022, Vol. 16, No. 4, pp. 271–291. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Biomeditsinskaya Khimiya.)
Databáze: MEDLINE
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