Generic Rapid Antiviral Screening Platform (GRASP)

The Covid-19 pandemic has exposed gaps in drug discovery capabilities specifically with respect to viral pathogens, such as SARS-CoV-2, but also revealed new opportunities for rapid repurposing of currently prescribed drugs as antiviral agents. The combined power of supercomputing, genomic platforms and machine learning based molecular docking (screening) algorithms provides scope for development of specialist screening platforms that can focus our best possible efforts on any viral pathogen of which the genome has been sequenced, including incorporation of new mutations that result in new viral strains.

Moleculomics is a life science technology company focused on genome scale computational modelling of receptor structure and drug docking, serving the pharmaceutical, health and biotech sectors. It has developed the Human3DProteome platform, the first technology to offer structurally-based open-ended lead discovery, pharmacological profiling and toxicity screening applied to every receptor in the human body; and Re-Drug, a comprehensive Artificial Intelligence-based screening technology for assessment of functionally feasible on-target and off-target interactions of a candidate therapeutic drawn from a pool of around 1400 FDA-approved drugs.

The proposed project involves the adaption of our existing repurposing platform and wider pharmacophore screening platform to targeting key proteins of SARS-CoV-2, moving forward from the current pandemic, and in effect, getting ahead of future outbreaks, by making the technology applicable to any virus and new strains evolving. An ambitious study at the Wellcome-Wolfson Institute for Experimental Medicine to screen 1000 FDA approved drugs and 500,000 drug combinations against the virus is underway. This project is fully complementary to that. The additional challenge is that the virus is mutating, though not particularly rapidly, still at about 26 mutations per year. It is likely in time that these mutations will affect viral structure, drug specificity and pathogenicity, opening up new opportunities for drug targeting and closing others. We are able to get ahead of the virus by modelling these new variants and structural changes before they happen by using our structural modelling pipelines to generate models of future coronavirus strains, and screen them against UK-approved drugs and wider chemical libraries. A further challenge is that the next global viral threat might not be a coronavirus, so there will be built-in future applicability to the other most threatening viruses, including influenza virus, on a "plug-and-play" basis. This will provide an invaluable rapid-reaction capability in industry and biomedical research for targeted drug discovery, which can incorporate screening of any chemical library against any virus.

The "Extension for Impact" funding will enhance the speed to market and extend the positive social and economic impacts of the GRASP platform by focussed collaboration with key partners and more widely publicised dissemination, in order to directly evaluate the best routes to market with specific collaborators and partners. This includes an Internet marketing campaign, beta testing, harmonising platform and data outputs with the needs of customers. The business model will be further developed, targeted towards drug repurposing, future drug development, specialist datasets, licensing opportunities and consultancy. The important scientific findings regarding repurposing opportunities for treatment of Covid-19 will be relayed to the relevant bodies.