Question

1. Knowing that the SARS viruses use ACE2 to infect cells, brainstorm possible pharmacological interventions that could exploit this relationship

Answer 1

SARS-CoV-2 and severe acute respiratory syndrome coronavirus (SARS-CoV) use ACE2 receptor to facilitate viral entry into target cells. Thus it is a prime target for pharmacological intervention on several disease fronts. Its identity was confirmed by showing that, when ACE2 was overexpressed in human cells non-permissive for viral infection, SARS-CoV entry and replication were facilitated; this process was blocked by an ACE2 antibody. Two unexpected features of ACE2 inhibitor binding arise from the structural studies-

1. First, inhibitor binding induced a large conformational change in the enzyme that aligns crucial residues for catalysis.

2. Second, the inhibitor binds to the enzyme in an inverse orientation from that predicted from the binding of the ACEI lisinopril to the active site of ACE