Understanding the pivotal roles of ACE2 in SARS-CoV-2 infection: from structure/function to therapeutic implication

In December 2019, a novel respiratory tract infection, from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in China that rapidly spread around the world. This virus possesses spike (S) glycoproteins on the surface of mature virions, like other members of coronaviridae. The S glycoprotein is a crucial viral protein for binding, fusion, and entry into the target cells. Binding the receptor-binding domain (RBD) of S protein to angiotensin-converting enzyme 2 (ACE 2), a cell-surface receptor, mediates virus entry into cells; thus, understanding the basics of ACE2 and S protein, their interactions, and ACE2 targeting could be a potent priority for inhibition of virus infection. This review presents current knowledge of the SARS-CoV-2 basics and entry mechanism, structure and organ distribution of ACE2, and also its function in SARS-CoV-2 entry and pathogenesis. Furthermore, it highlights ACE2 targeting by recombinant ACE2 (rACE2), ACE2 activators, ACE inhibitor, and angiotensin II (Ang II) receptor blocker to control the SARS-CoV-2 infection.