Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

Akbasheva O.E1, Spirina L.V.2, Dyakov D.A.1 , Masunova N.V.1

1. Siberian State Medical University, Tomsk, Russia
2. Siberian State Medical University, Tomsk, Russia; Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia
Section: Review
DOI: 10.18097/PBMC20226803157      PubMed Id: 35717581
Year: 2022  Volume: 68  Issue: 3  Pages: 157-176
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.
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Keywords: SARS-CoV-2, ACE2, TMPRSS, ADAM17, plasma proteases, α1-proteinase inhibitor

Akbasheva, O. E,, Spirina, L. V., Dyakov, D. A., Masunova, N. V. (2022). Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection. Biomeditsinskaya Khimiya, 68(3), 157-176.
This paper is also available as the English translation: 10.1134/S1990750822040035
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