The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19.

International Journal of Molecular Sciences
Alessandro BellisCarmine Morisco

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. Both these events trigger "cytokine storm" leading to acute lung and cardiovascular injury. A selective therapy for COVID-19 has not yet been identified. Clinical trials with remdesivir gave discordant results. Thus, healthcare systems have focused on "multi-targeted" therapeutic strategies aiming at relieving systemic inflammation and thrombotic complications. No randomized clinical trial has demonstrated the efficacy of renin angiotensin system antagonists in reducing inflammation related to COVID-19. Dexamethasone and tocilizumab showed encouraging data, but their use needs to be further validated. The still-controversial efficacy of these treatments highlighted the importance of organ injury prevention in COVID-19. Neprilysin (NEP) might be an interesting target for this purpose. NEP expression is increased by cytokines on lung fibroblasts surface. NEP activity is elevated in acute respiratory distress syndrome and it is conceivable that it is also high in COVID-19. NEP is implicated in the degradation of natriuretic pept...Continue Reading

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May 26, 2021·European Geriatric Medicine·Mariana AlvesUNKNOWN EuGMS Special Interest Group inCardiovascular Medicine (Chairpersons A. Ungar and A. Benetos)
Jun 18, 2021·Archives of Medical Research·Pariya KhodabakhshLeila Dargahi

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