COVID-19 preclinical drug development database
Name: Maria McPhillips
Email Address: firstname.lastname@example.org
A bottleneck for developing new therapeutics is the need for in vitro studies with fully infectious SARS-CoV-2 in competent human cells. These assays require molecular virology expertise combined with the necessary BSL3 biocontainment facilities. Linking drug screening pipelines with the capacity to identify possible in vitro resistance variants would also facilitate the prediction of drug-resistant strains that could circulate (or are already circulating) in vivo. The MRC-University of Glasgow Centre for Virus Research (CVR) has established CRUSH (COVID-19 Drug-Screening and Resistance Hub) for the benefit of the UK academic and industrial community. CRUSH is a facility fully dedicated to screen anti-SARS-CoV2 drugs/ monoclonal antibodies and characterise the potential drug-resistant mutations induced by possible lead compounds. CRUSH will also monitor the presence of SARS-CoV-2 globally circulating strains with potential drug-resistant mutations and curate an open access database with this information. In addition, CRUSH is also developing small rodent pre-clinical models for SARS-CoV-2. CRUSH has established pipelines for in vitro screening of antiviral compounds, and for the identification of drug-resistance variants. Indeed, to date we have carried out several antiviral screens in partnership with industrial and academic entities. We are very close to establishing pre-clinical small animal models for efficacy evaluation of promising antiviral compounds. CRUSH also has at its disposal a variety of relevant tools including a vast panel of antibodies to SARS-CoV-2 and related virus proteins, different human cell lines that express viral host entry factors, physiologically relevant three-dimensional (3D) organoid-based airway systems to study SARS-CoV-2 infections, and capability to generate by reverse genetics SARS-CoV-2 and related viruses carrying a variety of mutations of interest (particularly those found in the circulating variants). Such tools are invaluable in augmenting the activity of CRUSH.