Efficient modelling and validation of cryptic protein binding sites for drug discovery

To respond to the COVID19 emergency I have put together a project involving two colleagues at the School of Chemistry (Prof Hulme, Prof Barlow) of the University of Edinburgh to pursue a project entitled ''Fluorescent peptide binders of the SARS-CoV-2 Spike protein to accelerate development of COVID-19 diagnostics and drug therapies''. This project will be pursued in collaboration with colleagues in the School of Biological Sciences (Prof Auer) and the College of Medicine (Prof Dhaliwal). We wish to develop fluorescent probes to tag live SARS-CoV-2 virions that could be used for medical imaging and rapid point-of-care diagnostic applications. There is a real urgency to pursue this activity now. The Queens Medical Research Institute at the University of Edinburgh has formed the STOPCOVID research hub to exploit unique strengths in optical imaging technologies to monitor COVID-19 patient's lungs with an array of optical sensor probes. However, to date a fluorescent probe that selectively tags SARS-CoV-2 virions does not exist. Such optical probe would be extremely useful to assay drugs for their ability to prevent fusion of patient derived viral strains with host cells. It could also form the basis of cheap point-of-care biosensor technology to detect live viruses on surfaces. This could find immediate applications in decontamination of PPEs and clinical facilities, or as a diagnostic technology in LMIC countries that lack ready access to facilities with RT-PCR equipment and trained technical staff. Affordable and easily deployable testing worldwide will be essential to prevent future outbreaks from getting out of control.