ReviewProceedings of the National Academy of Sciences of the United States of America2020
Targeting the renin-angiotensin signaling pathway in COVID-19: Unanswered questions, opportunities, and challenges.
Review in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis.Microbial pathogenesis · 2022Pooled it
- Telmisartan reduces systemic inflammation and alters the renin-angiotensin system in mild COVID-19.Scientific reports · 2025Trial
- Article
- Human Lung Mast Cells as a Possible Reservoir for Coronavirus: A Novel Unrecognized Mechanism for SARS-CoV-2 Immune-Mediated Pathology.International journal of molecular sciences · 2024Article
- Review
- Identification of the regulatory mechanism of ACE2 in COVID-19-induced kidney damage with systems genetics approach.Journal of molecular medicine (Berlin, Germany) · 2023Article
- The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling.Vaccines · 2023Article
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Molecular docking analysis of AGTR1 antagonists.Bioinformation · 2023Article
- Molecular crosstalk between COVID-19 and Alzheimer's disease using microarray and RNA-seq datasets: A system biology approach.Frontiers in medicine · 2023Article
- Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions.Interdisciplinary sciences, computational life sciences · 2022Article
- In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.Cells · 2022Article
- Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.Molecules (Basel, Switzerland) · 2022Article
- Diminazene Aceturate Reduces Angiotensin II Constriction and Interacts with the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.Biomedicines · 2022Article
- Role of the renin-angiotensin system in NETosis in the coronavirus disease 2019 (COVID-19).Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- From COVID-19 to Sarcoidosis: How Similar Are These Two Diseases?Frontiers in immunology · 2022Review
- Discovery of a new generation of angiotensin receptor blocking drugs: Receptor mechanisms and in silico binding to enzymes relevant to SARS-CoV-2.Computational and structural biotechnology journal · 2022Article
- Article
- G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication.Journal of virology · 2021Article
- RAMIC: Design of a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of ramipril in patients with COVID-19.Contemporary clinical trials · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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 actions (e.g., activation of ACE2, agonism of MAS1 receptors, β-arrestin-based Angiotensin receptor agonists, and administration of soluble ACE2 or ACE2 peptides). Studies with animal models could test such approaches and assess therapeutic benefit. This Perspective highlights questions whose answers could advance RAS-targeting agents as mechanism-driven ways to blunt tissue injury, morbidity, and mortality of COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.