Possible Therapeutic Interventions in COVID-19 Induced ARDS by Cotinine as an ACE-2 Promoter and AT-1R Blocker

Author(s): Tarun Sharma, Sidharth Mehan*

Journal Name: Infectious Disorders - Drug Targets
Formerly Current Drug Targets - Infectious Disorders

Volume 21 , Issue 6 , 2021

Article ID: e170721189261
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Graphical Abstract:


In these challenging times of the pandemic, as coronavirus disease 2019 (COVID-19) has taken over the planet, its complications such as acute respiratory distress syndrome (ARDS) have the potential to wipe out a large portion of our population. Whereas a serious lack of ventilators, vaccine being months away makes the condition even worse. That's why promising drug therapy is required. One of them is suggested in this article. It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. ARDS can be assisted by angiotensin-II type-1 receptor (AT-1R) blocker and ACE-2 upregulator. AT-1R blocker will prevent vasoconstriction, the pro-inflammatory effect seen otherwise upon its activation. ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. Overall, decreased vasoconstriction of vessels supplying lungs and decreased vasodilation of lung tissues will ensure decreased pulmonary permeability and eventually relieve ARDS. It should also be considered that all components of the renin-angiotensin-aldosterone system (RAAS) are located in the lung tissues. A drug with the least plasma protein binding is required to ensure its distribution across these lung tissues. Cotinine appears to be a promising candidate for COVID-19- induced ARDS. It acts across the board and acts as both an AT-1R blocker, and ACE-2 upregulator. It also has a weak plasma protein binding that helps to spread through the lung tissues. In this review, we summarized that cotinine, along with COVID-19 virus replication blocker anti-virals, may prove to be a promising therapy for the treatment of COVID-19 induced ARDS.

Keywords: Coronavirus disease 2019 (COVID19), acute respiratory distress syndrome (ARDS), rennin angiotensin aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE-2), angiotensin-II, angiotensin-II type-1 receptor (AT-1R).

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Article Details

Year: 2021
Published on: 18 December, 2020
Article ID: e170721189261
Pages: 10
DOI: 10.2174/1871526520666201218153554
Price: $65

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