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

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.ACE2loaded 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.