High-Throughput Assay for Identifying Diverse Antagonists of the Binding Interaction between the ACE2 Receptor and the Dynamic Spike Proteins of SARS-CoV-2.

ABSTRACT: SARS-CoV-2, a coronavirus strain that started a worldwide pandemic in early 2020, attaches to human cells by binding its spike (S) glycoprotein to a host receptor protein angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the S protein and ACE2 has emerged as an important strategy for preventing viral infection. We systematically developed and optimized an AlphaLISA assay to investigate binding events between ACE2 and the ectodomain of the SARS-CoV-2 S protein (S-614G: residues 1-1208 with a D614G mutation). Using S-614G permits discovering potential allosteric inhibitors that stabilize the S protein in a conformation that impedes its access to ACE2. Over 30,000 small molecules were screened in a high-throughput format for activity against S-614G and ACE2 binding usin

SUBMITTER: Sammons RM 

PROVIDER: S-EPMC9673917 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature