Developing new drugs that activate the protective arm of the renin-angiotensin system as a potential treatment for respiratory failure in COVID-19 patients
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COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached pandemic proportions with negative impacts on global health, the world economy and human society. The clinical picture of COVID-19, and the fact that Angiotensin converting enzyme 2 (ACE2) is a receptor of SARS-CoV-2, suggests that SARS-CoV-2 infection induces an imbalance in the renin-angiotensin system (RAS). We review clinical strategies that are attempting to rebalance the RAS in COVID-19 patients by using ACE inhibitors, angiotensin receptor blockers, or agonists of angiotensin-II receptor type 2 or Mas receptor (MasR). We also propose that the new MasR activator BIO101, a pharmaceutical grade formulation of 20-hydroxyecdysone that has anti-inflammatory, anti-fibrotic and cardioprotective properties, could restore RAS balance and improve the health of COVID-19 patients who have severe pneumonia.
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Increased angiotensin-II levels and reduced angiotensin-(1-7) production due to lower ACE2 activity could provoke multiple COVID-19 symptoms, including vasoconstriction, thrombosis, inflammation, and potentially fatal respiratory failure.
“Increased levels of Ang-II and reduced production of Ang-1-7 due to the lower ACE2 activity could provoke multiple COVID-19 symptoms, including vasoconstriction, thrombosis, inflammation, and potentially fatal respiratory failure.14,18, 19, 20, 21”
An imbalance between levels of Ang-II and Ang-1-7 could provoke multiple pathophysiological features of COVID-19, including vasoconstriction, thrombosis, and inflammatory reaction.
“An imbalance between levels of Ang-II and of Ang-1-7 could provoke multiple pathophysiological features of COVID-19, including vasoconstriction, thrombosis, inflammatory reaction, which is potentially ultimately responsible for the respiratory symptoms observed during COVID-19.18, 19, 20, 21”
Restoring RAS balance either by inhibition of the classical arm or by stimulation of the protective arm would benefit patients with severe respiratory symptoms associated with COVID-19.
“Therefore, it has been suggested that restoring RAS balance either by inhibition of the classical arm of the RAS (ACE/Ang-II/AT1R) with classical ACE inhibitors or AT1R blockers (ARBs) or alternatively by stimulation of the protective arm of the RAS (ACE2/angiotensin 1-7/MasR axis) with AT2R or MasR activators would benefit patients with severe respiratory symptoms associated with COVID-19.18”
20E displays multiple beneficial pharmacological properties in humans, including anabolic, adaptogenic, hypoglycemic, antioxidant, anti-inflammatory, hepato- and cardioprotective, antihypertensive, anti-fibrotic, and anti-COVID properties.
“In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties, as well as cardio-, hepato-, and neuroprotective features.”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [3]
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Modulation of the renin-angiotensin system against COVID-19: A path forward?
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Self-citation
- Authors
- Latil, M., Camelo, S., Veillet, S., Lafont, R., & Dilda, P. J.
- Affiliations
- Sorbonne Université (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Dilda, Pierre J.
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 26
- Issue
- 5
- Pages
- 1311-1318
- ISSN
- 1359-6446 (ISSN-L)
- PMC
- PMC7888990
- OpenAlex
- W3132681628
- Cited by
- 31
- References
- 72
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 1 · 2021: 7
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- COVID-19 pandemic, SARS-CoV-2, renin-angiotensin system, ACE2, ACE inhibitors, angiotensin receptor blockers, angiotensin II type 2 receptor, Mas receptor, 20-hydroxyecdysone, respiratory failure, severe pneumonia, anti-inflammatory agents, antifibrotic agents, cardioprotection, drug repurposing
- MeSH terms
- Drug Development, COVID-19, SARS-CoV-2, Proto-Oncogene Mas, COVID-19 Drug Treatment, Angiotensin-Converting Enzyme Inhibitors, Animals, Ecdysone, Humans, Plant Extracts, Proto-Oncogene Proteins, Renin-Angiotensin System, Commelinaceae, Receptors, G-Protein-Coupled, Host-Pathogen Interactions, Angiotensin Receptor Antagonists
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