Targeting the renin-angiotensin signaling pathway in COVID-19: Unanswered questions, opportunities, and challenges.

Proceedings of the National Academy of Sciences of the United States of America
Krishna SriramPaul A Insel

Abstract

The role of the renin-angiotensin signaling (RAS) pathway in COVID-19 has received much attention. A central mechanism for COVID-19 pathophysiology has been proposed: imbalance of angiotensin converting enzymes (ACE)1 and ACE2 (ACE2 being the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] virus "receptor") that results in tissue injury from angiotensin II (Ang II)-mediated signaling. This mechanism provides a rationale for multiple therapeutic approaches. In parallel, clinical data from retrospective analysis of COVID-19 cohorts has revealed that ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be beneficial in COVID-19. These findings have led to the initiation of clinical trials using approved drugs that target the generation (ACEIs) and actions (ARBs) of Ang II. However, treatment of COVID-19 with ACEIs/ARBs poses several challenges. These include choosing appropriate inclusion and exclusion criteria, dose optimization, risk of adverse effects and drug interactions, and verification of target engagement. Other approaches related to the RAS pathway might be considered, for example, inhalational administration of ACEIs/ARBs (to deliver drugs directly to the lungs) and use of compounds with other...Continue Reading

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Jan 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiao Cong PangYi Zhun Zhu
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Jun 3, 2021·Viruses·P Brito-Zerón On Behalf Of The SarcoGEAS-Semi Registry

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