COVID-19 Drug-Screening and Resistance Hub (CRUSH)

Working in collaboration with LifeArc, MRC and Drug Discovery Unit (DDU) at the University of Dundee, the CVR created a translational hub for antiviral drug screening and resistance development. CRUSH is a fully integrated single-site hub with biocontainment facilities and expertise dedicated to accelerating antiviral therapeutic discovery for SARS-CoV-2 and other high consequence viruses requiring BSL2 (CL2) & BSL3 (CL3) containment. It is a one-stop facility with capabilities to perform medium- to high-throughput screens of antivirals, serology/virus neutralisation assays, hit validations in primary cultures and against panels of variant viruses, kinetic assays, assays to determine genetic barrier to resistance to selected hits, real-time monitoring of emerging mutations, and finally efficacy evaluations in pre-clinical small animal models. We will develop the newly established CRUSH platform as a vehicle for translation in the CVR and to boost our engagement with industry, but also to interface with the CVR’s Preparedness Platform. Established with funding from LifeArc and the MRC, CRUSH is a translational hub, facilitating the CVR’s interface with industry. It is a one-stop, self-sustaining facility designed to aid pre-clinical development of antiviral drugs against SARS-CoV-2 and other viruses requiring CL3 containment. Over the next quinquennium, we will further develop high-throughput assays that can be performed at both CL2 and CL3 levels to increase the capacity of the facility, and the use of experimental animal models. Specifically, CRUSH conducts drug screening and neutralisation assays for SARS-CoV-2 including alpha, beta, gamma, delta, omicron variants and new variants as they arise. New assays have been developed for monkeypox (Mpox) virus and influenza A. Other viral targets currently included under development for screening services include seasonal coronaviruses, influenza A/B, RSV, enteroviruses, rotavirus and arboviruses. CRUSH will support the implementation of a quality management system and integration of laboratory information management system (LIMS) encompassing an ELN/Bio-registry, to support data integrity and management. Additionally, the optimisation and development of a high-throughput screening system and completion/publication of in vivo models and exemplar studies. Our animal licence has now been extended to encompass transmission studies, vaccines/immunomodulators and flow cytometry and we intend to extend this further to include Mpox virus and anti-viral drug evaluation. The long-term goal of CRUSH is to create a stable and sustainable resource for the UK’s academic and industrial community to help accelerate drug discovery for any known or novel high consequence virus requiring high containment facilities.