Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022;16(4):271-291.
doi: 10.1134/S1990750822040035. Epub 2022 Nov 16.

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

O E Akbasheva  1 , L V Spirina  1   2 , D A Dyakov  1 , N V Masunova  1
Affiliations

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

O E Akbasheva et al. Biochem Mosc Suppl B Biomed Chem. 2022.

Abstract

The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α1-PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α1-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 α1-PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α1-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 α1-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 α1-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 α1-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.

Keywords: ACE2; ADAM17; SARS-CoV-2; TMPRSS; plasma proteases; α1-proteinase inhibitor.

PubMed Disclaimer

Conflict of interest statement

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.

Similar articles

See all similar articles

Cited by

References

    1. Ghahramani S., Tabrizi R., Lankarani K.B. S.M., Rezaei, S., Zeidi, N., Akbari, M., Heydari, S.T., Akbari, H., Nowrouzi-Sohrabi, P., and Ahmadizar, F. Eur. J. Med. Res. 2020;25:30. doi: 10.1186/s40001-020-00432-3. - DOI - PMC - PubMed
    1. Wang, F., Hou, H., Wang, T., Luo, Y., Tang, G., Wu, S., Zhou, H., and Sun, Z., Travel. Med. Infect. Dis., 2020, vol. 36, p. 101782. 10.1016/j.tmaid.2020.101782 - PMC - PubMed
    1. Abdelrahman Z., Li M., Wang X. Front. Immunol. 2020;11:552909. doi: 10.3389/fimmu.2020.552909. - DOI - PMC - PubMed
    1. Azer S.A. New Microbes New Infect. 2020;37:100738. doi: 10.1016/j.nmni.2020.100738. - DOI - PMC - PubMed
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7. - DOI - PMC - PubMed

LinkOut - more resources