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Review
. 2022 Feb 8:2022:7423537.
doi: 10.1155/2022/7423537. eCollection 2022.

Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19

Affiliations
Review

Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19

Aisha Tabassum et al. Mediators Inflamm. .

Abstract

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Bradykinin synthesis and degradation.
Figure 2
Figure 2
Role of ACE2 and ACE in the renin angiotensin system and kinin system.
Figure 3
Figure 3
Pathogenesis of COVID-19 through bradykinin pathway.

References

    1. Jin Y., Yang H., Ji W., et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses . 2020;12(4):p. 372. doi: 10.3390/v12040372. - DOI - PMC - PubMed
    1. Lu R., Zhao X., Li J., et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet . 2020;395(10224):565–574. doi: 10.1016/S0140-6736(20)30251-8. - DOI - PMC - PubMed
    1. Meini S., Zanichelli A., Sbrojavacca R., et al. Understanding the pathophysiology of COVID-19: could the contact system be the key? Frontiers in Immunology . 2020;11:2014–2014. doi: 10.3389/fimmu.2020.02014. - DOI - PMC - PubMed
    1. Lai C. C., Shih T. P., Ko W. C., Tang H. J., Hsueh P. R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. International Journal of Antimicrobial Agents . 2020;55(3, article 105924) doi: 10.1016/j.ijantimicag.2020.105924. - DOI - PMC - PubMed
    1. Nikolich-Zugich J., Knox K. S., Rios C. T., Natt B., Bhattacharya D., Fain M. J. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. GeroScience . 2020;42(2):505–514. doi: 10.1007/s11357-020-00186-0. - DOI - PMC - PubMed