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• W4283160183 endingPage "176" @default.
• W4283160183 startingPage "157" @default.
• W4283160183 abstract "The SARS-CoV-2 pandemia had stimulated the numerous publications emergence on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), primarily when it was found that high mortality in some regions corresponded to the regions with deficient α1-PI alleles. By analogy with the last century's data, when the root cause of the α1-antitrypsin, genetic deficiency leading to the elastase activation in pulmonary emphysema, was proven. It is evident that proteolysis hyperactivation in COVID-19 may be associated with α1-PI impaired functions. The purpose of this review is to systematize scientific data, critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a target in therapy. This review describes the proteinase-dependent stages of a viral infection: the reception and virus penetration into the cell, the plasma aldosterone-angiotensin-renin, kinins, blood clotting systems imbalance. The ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases role in the virus tropism, proteolytic cascades activation in blood, and the COVID-19-dependent complications is presented. The analysis of scientific reports on the α1-PI implementation in the SARS-CoV-2-induced inflammation, the links with the infection severity, and comorbidities were carried out. Particular attention is paid to the acquired α1-PI deficiency in assessing the patients with the proteolysis overactivation and chronic non-inflammatory diseases that are accompanied by the risk factors for the comorbidities progression, and the long-term consequences of COVID-19 initiation. Analyzed data on the search and proteases inhibitory drugs usage in the bronchopulmonary cardiovascular pathologies therapy are essential. It becomes evident the antiviral, anti-inflammatory, anticoagulant, anti-apoptotic effect of α1-PI. The prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders are presented.Pandemiia koronavirusnoĭ infektsii dala stimul poiavleniiu mnogochislennykh publikatsiĭ, posviashchennykh α1-proteinaznomu ingibitoru (α1-PI, α1-antitripsin), osobenno kogda bylo vyiavleno, chto vysokaia smertnost' naseleniia nekotorykh regionov sootvetstvuet geograficheskoĭ lokalizatsii defitsitnykh alleleĭ α1-PI. Po analogii s dannymi proshlogo stoletiia, kogda byla dokazana pervoprichina geneticheskogo defitsita α1-antitripsina, privodiashchaia k aktivatsii élastazy pri émfizeme legkikh, mozhno predpolozhit', chto giperaktivatsiia proteoliza pri COVID-19 sviazana s narusheniem funktsionirovaniia α1-PI. Tsel' nastoiashchego obzora zakliuchaetsia v sistematizatsii nauchnykh dannykh o roli α1-PI kak diagnosticheskogo markera i/ili sredstva targetnoĭ terapii v usloviiakh giperaktivatsii proteoliza pri infitsirovanii SARS-CoV-2 i opredelenii kliuchevykh napravleniĭ transliatsionnykh issledovaniĭ ingibitorov proteinaz. V rabote dana kharakteristika proteinazozavisimykh stadiĭ virusnoĭ infektsii: retseptsiia i proniknovenie virusa vnutr' kletki, disbalans angiotenzin-reninovoĭ, kininovoĭ, svertyvaiushcheĭ i fibrinoliticheskoĭ proteoliticheskikh sistem plazmy krovi. Rassmotrena rol' angiotenzinprevrashchaiushchego fermenta 2 (ACE2), membrano-sviazannoĭ serinovoĭ proteazy (TMPRSS), metalloproteazy ADAM17, furina, katepsinov, tripsino- i élastazopodobnykh serinovykh proteinaz v reguliatsii tropnosti virusa, aktivatsii proteoliticheskikh kaskadov plazmy krovi, razvitii oslozhneniĭ koronavirusnoĭ infektsii. Proveden analiz dannykh po uchastiiu α1-PI v patogeneze koronavirusnoĭ infektsii, vzaimosviazi so stepen'iu tiazhesti COVID-19 i komorbidnymi zabolevaniiami. Osoboe vnimanie udeleno roli priobretennogo defitsita α1-PI pri otsenke sostoianiia bol'nykh v usloviiakh giperaktivatsii proteoliza na fone khronicheskikh zabolevaniĭ, formirovaniia faktorov riska progressirovaniia soputstvuiushcheĭ patologii i razvitiia otdalennykh posledstviĭ COVID-19. Pronalizirovany dannye po poisku i primeneniiu lekarstvennykh sredstv, obladaiushchikh ingibitornoĭ aktivnost'iu pri terapii zabolevaniĭ bronkholegochnoĭ, serdechno-sosudistoĭ sistem. Predstavleny dokazatel'stva nalichiia protivovirusnogo, protivovospalitel'nogo, antikoaguliantnogo, antiapoptoticheskogo éffekta α1-PI i perspektiv ispol'zovaniia ego v kachestve targetnogo preparata pri lechenii koronavirusnoĭ infektsii." @default.
• W4283160183 created "2022-06-21" @default.
• W4283160183 creator A5013827758 @default.
• W4283160183 creator A5028519233 @default.
• W4283160183 creator A5063597155 @default.
• W4283160183 creator A5065457299 @default.
• W4283160183 date "2022-01-01" @default.
• W4283160183 modified "2023-10-11" @default.
• W4283160183 title "Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection" @default.
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