Title:Natural Agents Modulating ACE-2: A Review of Compounds with Potential against SARS-CoV-2 Infections
Volume: 27
Issue: 13
Author(s): Arquimedes Gasparotto Junior*, Sara Emília Lima Tolouei, Francislaine Aparecida dos Reis Lívero, Francielli Gasparotto, Thaise Boeing and Priscila de Souza
Affiliation:
- Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS,Brazil
Keywords:
Alkaloids, Covid-19, flavonoids, natural products, phenolic compounds, terpenoids.
Abstract: One of the biggest challenges of public health worldwide is reducing the number of events and
deaths related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The angiotensinconverting
enzyme 2 (ACE-2), a carboxypeptidase that degrades angiotensin II into angiotensin 1-7, has been
identified as a potent receptor for SARS-CoV-2. In the last decades, ACE inhibition has assumed a central role
in reducing cardiovascular and renal events. However, with the advent of COVID-19, attention has been turned
to ACE-2 as a possible target to reduce virus binding to different human cells. This review aims to discuss recent
developments related to the medicinal properties of natural compounds as ACE/ACE-2 inhibitors, which
should be highlighted in the future development of studies looking for modulators in SARS-CoV-2 infection.
Data show that bioactive compounds isolated from several natural products act by inhibiting ACE/ACE-2,
which changes the entire axis of this system. Of the compounds addressed in this review, 7 phenolic compounds,
including quercetin, curcumin, naringenin, luteolin, hesperidin, mangiferin, and gallic acid showed
binding affinity with molecular ACE-2 target in silico, and 1, esculetin, decreased ACE-2 expression in vivo.
Regarding terpenoids and alkaloids, nimbin, withaferin A, andrographolide, zingiberene and, berberine,
piperine and thebaine, respectively, showed a binding affinity with molecular ACE-2 target in silico. These findings
reinforce the need for future preclinical and clinical studies on these compounds and specific inhibitory effects
on ACE-2 of all the other compounds described herein only as nonspecific ACE inhibitors. It is important
to mention that some natural compounds such as magnolol, resveratrol, rosmarinic acid, tanshinone IIA, and nicotine
have also demonstrated the potential to increase the activity or expression of ACE-2, and could therefore
aggravate SARS-CoV-2 infection.
