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Volume 25, Issue 7
  • ISSN: 1871-5265
  • E-ISSN: 2212-3989
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Abstract

Introduction

Over the past four years, SARS-CoV-2 and COVID-19 have become global health crises, spurring extensive research on virus behavior, complications, and treatments. The virus interacts with a component of the renin-angiotensin system (RAS), altering inflammatory, hypertrophic, and hemodynamic responses binding to ACE2 found in organs like the heart, lungs, and kidneys.

Objective

This review explores the RAS-COVID-19 interplay, focusing on key molecules like ACE2, Ang-(1-7), and Ang-(1-9), influencing susceptibility, severity, and treatments. It seeks to clarify ACE2's dual role in viral entry and protection and assess the therapeutic potential of balancing Ang-(1-7) and Ang-(1-9) to prevent disease progression and related complications.

Methods

Studies were chosen through a systematic search in databases, such as PubMed, Scopus, and Web of Science. The inclusion criteria were centered on peer-reviewed research that explored the relationship between SARS-CoV-2 and important RAS molecules, including ACE2, Ang-(1–7), and Ang-(1-9), seeking information on therapies, severity, and susceptibility. Non-peer-reviewed articles and those lacking focus on RAS-COVID-19 interplay were excluded. Titles and abstracts were screened, followed by full-text assessment and data extraction for analysis.

Results

Some studies indicate that the peptides Ang-(1-7) and Ang-(1-9) could provide protective effects against heart-related complications by counteracting the harmful impacts of the angiotensin II pathway, which is often exacerbated by SARS-CoV-2. Ang-(1-7) and Ang-(1-9) are recognized for promoting vasodilation, reducing inflammation, and preventing fibrosis, which can mitigate the heart damage typically associated with COVID-19.

Discussion

ACE2, a component of the non-canonical RAS, is closely linked to SARS-CoV-2 and plays a pivotal role in the pathophysiology of COVID-19. Ang-(1-9) and Ang-(1-7) are produced by ACE2 and have demonstrated positive cardiovascular effects. In the context of COVID-19, Ang-(1-7) has shown protective effects in preclinical studies and clinical trials; however, more evidence is needed to support this effect.

Conclusion

Further research, including clinical trials, is vital to understand and develop precise therapies for COVID-19 and similar infectious diseases.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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The Counter-Regulatory Renin-Angiotensin System: A Surprising Ally in the Field of COVID-19
Infect. Disord. Drug Targets 25, E18715265352715 (2025); https://doi.org/10.2174/0118715265352715250717101135
/content/journals/iddt/10.2174/0118715265352715250717101135
/content/journals/iddt/10.2174/0118715265352715250717101135
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  • Article Type:     Review Article
Keyword(s): angiotensin (1-7); angiotensin (1-9); angiotensin conversion enzyme type 2; COVID-19; renin-angiotensin system; renin-angiotensin-aldosterone system; SARS- CoV-2

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