COVID-19: Annotating and controlling the inter-species protein interactome through the development of peptide inhibitors for SARS-CoV-2 and human protein interactions

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The novel coronavirus pandemic has collectively re-focused the research community towards a collaborative investigation of the SARS-CoV-2 virus and discovery of the mechanisms supporting COVID19 manifestation in humans. Research on the novel coronavirus has progressed with unprecedented speed due, in large part, the rapid determination of the SARS-CoV-2 genome and proteome. Promisingly, many computational approaches have also been deployed to increase our understanding of SARS-CoV-2, including the prediction of protein function, three-dimensional protein structure, and possible therapeutic targets for existing small inhibitory molecules. Given that the Spike protein from the original SARS coronavirus, SARS-CoV, is known to interact with the human Angiotensin-Converting Enzyme 2 (hACE2), much of the current research effort is focused to better characterize the SARS-CoV-2 Spike protein and its putative interaction with the ACE2 protein; a critical protein-protein interaction necessary for host infection. Similar efforts are being made to understand the functional and evolutionary characteristics of the SARS-CoV-2 proteome, including the determination of evolutionary conserved functional regions between related viruses to inform the use of anti-viral therapeutics. Given the unique infectivity characteristics of this novel coronavirus, the need for an effective strategy of anti-viral development is pressing. The long viral incubation period, during which an individual is simultaneously contagious and asymptomatic, has resulted in rapid global proliferation. Leveraging what is known from the original SARS-CoV outbreak, circa. 2003, and related viral families, this proposal contributes to our understanding of the viral inter-species protein interaction network. Together with Zim Corporation, a Canadian company with software and peptide biopharmaceutical experience, our cross-disciplinary team will use algorithms co-developed by co-applicants Biggar and Green to study the novel coronavirus and to produce novel peptide-based anti-viral drugs that antagonize interactions deemed critical to the virus-host interaction. Further, not only will this research develop potential anti-viral peptides for COVID19 treatment, but also establish an innovative resource for anti-viral peptide development as new viruses are introduced to the human population.