Alternative attacks against SARS-CoV-2 proteins: Identifying and developing orthogonal therapeutic strategies using computational structural biology and synthetic chemistry

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This project is a collaboration between the Trant research group at the University of Windsor, which focuses on computational and synthetic medicinal chemistry (with particular focus on the development of cyclic peptide and carbohydrate-based therapeutics); and Devonian Health Group (DHG), a Montreal-based pharmaceutical company. SARS-CoV-2, the causative agent for COVID-19, is essentially a self-replicating machine made up of proteins and lipids. The proteins have all been identified, and recent work has shown that many of them interact with human proteins when they are in an infected cell. These interactions could provide the basis for designing drugs that can bind to the SARS-CoV-2 proteins, preventing them from doing their job. Many of the immediate efforts are aimed at repurposing approved drugs, but the SARS-CoV-2 proteins are very different from the normal targets of these drugs; one of the major challenges is that these proteins lack well-defined pockets and clefts that are the normal targets of normal drugs, and many are coated in sugars that make the surface challenging to access for antibodies and drugs. However, they are perfect targets for unconventional approaches such as cyclic peptides and repurposed proteins. The Trant group is using a combination of computational modeling to understand the interactions between these proteins and small molecules with the eventual dual goals of developing therapeutics and providing a better understanding of SARS-CoV-2 molecular biology. Trant and DHG already have an active collaboration in antimicrobial science and will be leveraging this connection to further investigate and develop any molecules identified by the team. SARS-CoV-2 is a challenging target, and we will need to explore all options for treatment, including innovative biologics that we will be investigating in this project, so that we as Canadians can safely and confidently resume our normal lives.