ABSTRACT
The COVID-19 pandemic, caused by SARS-CoV-2, is a pressing public health emergency garnering 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-ACE2 interaction is a potential therapeutic target for treating COVID-19. We have developed a proximity-based AlphaLISA assay to measure binding of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) to ACE2. Utilizing this assay platform, a drug-repurposing screen against 3,384 small molecule drugs and pre-clinical compounds was performed, yielding 25 high-quality, small-molecule hits that can be evaluated in cell-based models. 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.
Subject(s)
COVID-19ABSTRACT
The National Center for Advancing Translational Sciences (NCATS) has developed an online open science data portal for its COVID-19 drug repurposing campaign - named OpenData - with the goal of making data across a range of SARS-CoV-2 related assays available in real-time. The assays developed cover a wide spectrum of the SARS-CoV-2 life cycle, including both viral and human (host) targets. In total, over 10,000 compounds are being tested in full concentration-response ranges from across multiple annotated small molecule libraries, including approved drug, repurposing candidates and experimental therapeutics designed to modulate a wide range of cellular targets. The goal is to support research scientists, clinical investigators and public health officials through open data sharing and analysis tools to expedite the development of SARS-CoV-2 interventions, and to prioritize promising compounds and repurposed drugs for further development in treating COVID-19.