Allosteric Binders of ACE2 Are Promising Anti-SARS-CoV-2 Agents.

ABSTRACT: The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for acute treatment of the disease. We investigate whether compounds that bind the human angiotensin-converting enzyme 2 (ACE2) protein can decrease SARS-CoV-2 replication without impacting ACE2's natural enzymatic function. Initial screening of a diversity library resulted in hit compounds active in an ACE2-binding assay, which showed little inhibition of ACE2 enzymatic activity (116 actives, success rate ∼4%), suggesting they were allosteric binders. Subsequent application of in silico techniques boosted success rates to ∼14% and resulted in 73 novel confirmed ACE2 binders with K _d v

SUBMITTER: Hochuli JE 

PROVIDER: S-EPMC9236207 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature