PMC:7408073 / 104683-106651 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7408073","sourcedb":"PMC","sourceid":"7408073","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7408073","text":"As already mentioned, chelating agents, by limiting zinc cellular availability, might influence hyperactivity, synthesis and conformation of both ACE2 and ACE, which may impair not only ACE2 (and ACE) enzymatic activity but also its availability on cell surface for viral entry. For these reasons, chelating agents might be effective to counter SARS-CoV-2 infection, and in particular when (e.g., induced by hypoxia) both arms of the RAS are likely upregulated. Differently from renin inhibitors, more chelating agents are commercially available and both classes of drugs might be administered, alone or in combination with other therapies for COVID-19. Of note, these classes of drugs might be beneficial not only for SARS-CoV-2 infection but also for other disease in which both arms of the RAS (and of the inflammatory system) are upregulated, as for example ARDS, PAH and other pathologies associated to chronic hypoxia and cardiac failure. Indeed, both Ang-II and Ang-(1–7) upregulation and a cytokine storm are common aspects in patients not only with ARDS and PAH but also with critical coronary artery disease [182], suggesting an upregulation of both arms of the RAS and of the inflammatory system in several different dysfunctions. Notably, a number of clinical trials have indicated the utility of CaNa2EDTA in coronary heart disease. It was believed that chelation therapy might alter plaque morphology and volume, or improve endothelial function [123]. However, the evidence was not convincing [123]. Future clinical trials on selected patients with both ACE and ACE2 upregulation might be more convincing. It is clear that similar pathways of activation can lead to different outcomes depending on individual predisposition/background. Therefore, future efforts to understand the genetic, morpho-physiological, environmental and lifestyle factors that individually affect the predisposition to a specific disease with a precision medicine must be 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