Integration of genomics and AI to accelerate drug discovery against COVID-19 [Funder: Genome Quebec, IRIC, McMaster University, Mila]

The COVID-19 pandemic urgently requires new therapeutics against the causative SARS-CoV-2 coronavirus. In the short term, new antiviral drugs will be required to ameliorate the COVID-19 crisis, while in the long term a suite of antivirals directed against coronavirus pathogens will allow better preparedness against future pandemics. However, conventional approaches to drug discovery take a decade or more and must be expedited to have an impact on the pandemic. This initiative will combine functional genomics, artificial intelligence (AI) and advanced medicinal chemistry to accelerate the discovery of drugs that interdict the SARS-CoV-2 virus lifecycle. The proposed project will undertake three coupled activities: 1. Systematic genetic analysis of host cell vulnerabilities for SARS-CoV-2 replication using CRISPR-based functional genomic screening technology; 2. Ultra-high throughput AI-based computational design of small molecule ligands for viral and host target proteins; 3. Synthesis of top tractable AI screen hits and validation in biochemical, cell-based and animal model contexts. The main outputs from theseactivities will be the first systematic network of virus-host cell genetic interactions, a comprehensive set of target genes and processes for antiviral drug discovery, a state-of-the-art AI pipeline for prediction of high affinity small molecule-target interactions and proof-of-concept for a set of candidate small molecule inhibitors of viral replication.These outputs will generate corresponding intellectual property that will be of interest to a variety of commercial partners and will potentially form the foundation for a spin-out company in AI-based drug discovery. The long-term vision of the project is to transform the drug development pipeline across all disease areas.