ACE-2, TMPRSS2 and Beyond; Promising Targets and Tools for COVID-19 Prophylaxis and Treatment

Abstract

Several repurposing drugs and ongoing vaccine researches tocombat Coronavirus Disease-19 (COVID-19) are testing clinically,worldwide. COVID-19 caused by severe acute respiratory failuresyndrome-CoV-2, uses angiotensin-converting enzyme 2 (ACE-2) as a functional receptor for entry into the cells, followed by itspriming by transmembrane protease serine 2 (TMPRSS2). Most ofthe ACE-2 expressing cells are alveolar type II pneumocytes. ViralS-glycoprotein, TMPRSS2 and ACE-2 inhibition, as extracellularmedia components, are potential targets of future therapy. ACE-2 and/or TMPRSS2 blockade is thought to be beneficial in theprevention or treating of this infection which will be the mostconvenient for pharmacoeconomics and effectiveness, regardingsimilar future pandemics. Despite substrate-based design andsynthesis of ACE-2 inhibitor compounds were presented almosttwo decades ago, data on renin angiotensin system activation orits blockers, especially ACE-2, are limited by now. Priority mustbe given to design a convenient vaccine soon, but due to the highmutation ability of such viruses mean that new vaccines may needto be developed for each outbreak. So, de novo drugs such as ACE-2or TMPRSS2 blockers need to be developed which can specificallyblock spike binding sites of the target cells and prevent virusintrusion, especially at the extracellular media, for future pandemics.