The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to actionto uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir's discovery, mechanism of action, and the current studies exploring its clinical effectiveness.
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.
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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