Interactions between ACE2 and SARS-CoV-2 S Protein: Peptide Inhibitors for Potential Drug Developments Against COVID-19

Angiotensin-converting enzyme (ACE) shares some homologies with ACE2. However, they are not inhibited by the same inhibitors, but both are associated primarily with the hypertensive disorder through the renin-angiotensin system (RAS). The principal activity of ACE2 is to metabolize Ang II into the vasodilatory Ang-(1-7). The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought the ACE2 to the center of attention. This coronavirus uses the host cell ACE2 protein to enter and infect the epithelial cells. In light of the virus's entrance into human cells, the differences in the molecular basis of ACE2 among affected patients may cause their different responses to the virus. Many details about the specific interaction between the viral S protein and ACE2 are already reported. To date, some effective clinically approved vaccines are in use globally, and many others are under development, but no effective specific therapeutic drugs are available against COVID-19. Inhibitors, especially peptide inhibitors, have a great potential to be used for the treatment of COVID-19 and other possible emerging diseases caused by viral pathogens. As a result of the well-known viral protein structures and their host cell targets such as ACE2, antiviral peptides could be appropriately designed and optimized for therapeutic purposes. A better understanding of the structure and pathophysiology of the ACE2 receptor and the interplay between the viral S protein and ACE2 may help to find the solution for the virus treatment. This review summarizes the current understanding of S protein interaction with the ACE2 protein as a potential specific target against SARS-CoV-2 and strategies using peptides against COVID-19.