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[Image: see text] The COVID-19 pandemic, caused by SARS-CoV-2, is a pressing public health emergency garnering a rapid response from scientists across the globe. Host cell invasion is initiated through direct binding of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Disrupting the spike protein–ACE2 interaction is a potential therapeutic target for treating COVID-19. We have developed a proximity-based AlphaLISA assay to measure the binding of SARS-CoV-2 spike protein receptor binding domain (RBD) to ACE2. Utilizing this assay platform, a drug-repurposing screen against 3384 small-molecule drugs and preclinical compounds was carried out, yielding 25 high-quality primary hits, of which only corilagin was validated in cherry-picking. This established AlphaLISA RBD–ACE2 platform can facilitate evaluation of biologics or small molecules that can perturb this essential viral–host interaction to further the development of interventions to address the global health pandemic.
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document_parses/pdf_json/9626183a8899364f557c5fce53629a8e18a23112.json
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document_parses/pmc_json/PMC7688046.xml.json
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Targeting ACE2–RBD Interaction as a Platform for COVID-19 Therapeutics: Development and Drug-Repurposing Screen of an AlphaLISA Proximity Assay
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