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Renin-angiotensin system at the heart of COVID-19 pandemic

Marco Alifano 1, 2, * Pietro Alifano 3 Patricia Forgez 4 Antonio Iannelli 5, 6 
* Corresponding author
2 Cancer, Immune Control, and Escape [Paris]
CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
4 Homéostasie Cellulaire, Cancer et Thérapies [Paris]
T3S - UMR_S 1124 - Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire
6 Hepatic Complications of Obesity [Nice]
C3M - Centre méditerranéen de médecine moléculaire
Abstract : Significant aspects of COVID-19 pandemic remain obscure. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID-19. We strongly encourage the concept that thorough considerations of receptor-ligand interactions should be kept at the heart of scientific debate on infection. In this idea, the whole renin-angiotensin system has to be evaluated. We hypothesize that factors related to ethnicity, environment, behaviors, associated illness, and medications involving this complex system are probably responsible for situations regarded as anomalous from both an epidemiological and a clinical point of view, but, taken together, such factors may explain most of the aspects of current outbreak. We decided to use the analogy of a play and speculate about the possible impact in this tragedy of 1) air pollution via the interference of nitrogen dioxide on ACE2 expression; 2) the dual role of nicotine; 3) the hypothetical involvement of ACE2 polymorphisms, the relationships of which with ethnic factors and susceptibility to cardiovascular disease seems intriguing; 4) the impact on the severity of infection of hypertension and related medications acting on the renin/angiotensin system, and, finally, 5) the possible helpful role of chloroquine, thanks to its capacity of modifying ACE2 affinity to the viral spike protein by altering glycosylation. This hypothesis paper is an urgent call for the development of research programs that aim at questioning whether the putative protagonists of this tragedy are real-life actors in COVID-19.
Keywords : ACE2 COVID-19 Mechanisms
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Submitted on : Friday, May 20, 2022 - 10:24:11 AM
Last modification on : Wednesday, September 28, 2022 - 4:20:12 PM


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Marco Alifano, Pietro Alifano, Patricia Forgez, Antonio Iannelli. Renin-angiotensin system at the heart of COVID-19 pandemic. Biochimie, Elsevier, 2020, 174, pp.30-33. ⟨10.1016/j.biochi.2020.04.008⟩. ⟨inserm-02566815⟩



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