Advances in Angiotensin Converting Enzyme-2 and Renin Angiotensin System Against COVID 19: A Pharmacotherapy and Physicochemical Review

Abstract

The renin-angiotensin-aldosterone system (RAAS) is a key regulator of cardiovascular function through components like angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7). Angiotensin-converting enzyme (ACE) plays a pivotal role, existing as ACE1 and ACE2 isoforms. The COVID-19 pandemic, resulting from coronavirus, exploits ACE2 for cell entry, leading to a global outbreak. The virus's impact on ACE2 and the RAAS system influences disease severity. This review concentrates on the interplay between ACE2, RAAS, and SARS-CoV-2, investigating viral entry, binding patterns, and effects on RAAS balance. The virus binds to ACE2's receptor-binding domain (RBD) and enters cells via endocytosis, involving TMPRSS2 protease. SARS-CoV-2's higher ACE2 affinity contributes to its infectivity. ACE2 expression varies in health and disease, impacting COVID-19 outcomes. The RAAS has two opposing arms—classical and counter-regulating. ACE2 bridges these arms, converting Ang II to Ang 1–7 with vasodilatory and protective effects. The pandemic introduces a "third arm," the RAAS-SARS-CoV-2-axis, impacting ACE2 expressions and RAAS balance. Recombinant ACE2 (hrsACE2) shows promise in inhibiting viral replication and reducing viral load. ACE2-loaded extracellular vesicles (EVs) extend ACE2's effectiveness, inhibiting virus infectivity. Immunological factors such as cytokines, interferons, and cell count influence COVID-19 severity. Understanding ACE2's role and its interactions with RAAS and SARS-CoV-2 is vital for potential therapeutic strategies and disease management.