Fluorescent stapled peptides that selectively recognise the SARS-CoV-2 spike protein

We have recently developed a computational platform for the design of constrained (stapled) peptides. In response to the COVID-19 pandemic, we have applied this ‘Stapline’ platform to the in silico design of stapled peptides that selectively recognise the “Spike” protein on the SARS-CoV-2 virus, using University of Edinburgh resources and compute time donated by Amazon web services. Such molecules are urgently needed to support COVID-19 optical medical imaging efforts at the Queen’s Medical Research Institute (QMRI). In this project, we will outsource the synthesis of the optimised fluorophore-labelled stapled peptides identified using our ‘Stapline’ platform, to companies that have remained open during the pandemic. Once made, we will compare the binding affinity of these fluorescent, stapled peptides to the SARS-CoV-2 virus against known (lower affinity, protease sensitive) peptide binding sequences in biophysical and cell-based assays. High affinity, protease resistant, Spike-protein specific, fluorescent, stapled peptide probes identified by this project will be applied in imaging virus fusion of wild-type and patient-derived strains in new containment facilities at QMRI. This work will also accelerate development of inexpensive and easily deployable biosensing technologies to detect SARS-CoV-2 virions on surfaces, and for point-of-care diagnostics.