The Toronto Open Access COVID-19 Protein Manufacturing Center [Funder: University of Toronto]

The virus causing COVID-19, SARS-CoV-2, encodes 25 proteins in its genome. Collectively, these proteins are responsible for all viral pathogenic functions, including cellular attachment and infiltration, translation of the viral RNA genome into the viral proteins, immune system evasion, assembly of new virions, and escape from the host cell. Most if not all of these proteins are under intense investigation by organizations world-wide into their basic biochemistry/biology, as targets for novel antiviral compounds, as targets for viral neutralizing antibodies, as reagents for diagnostics, and for vaccine development. A foundational component for all of these initiatives is access to high-quality purified viral protein. Since 2013, our group has been part of an NIAID (NIH)-funded project called Center for Structural Genomics of Infectious Diseases (CSGID, https://csgid.org/). The mandate of CSGID is to purify proteins of relevance to biodefence and pandemics, and solve their crystal structures. As a part of this, we in Toronto have already purified 9 SARS-CoV-2 proteins and are acquiring the clones for all 25 from our partners at CSGID. We have deposited two SARS-CoV-2 structures in the Protein Data Bank (6W4H, 6W75). This proposal has two aims. First, we will focus on methyltransferase (nsp10/16 complex) drug discovery (with Takeda and CSGID). Second, our protein purification team will produce large quantities of pure viral proteins in a rapid fashion for distribution to any Canadian business or academic. Since making these intentions known to the community (March 30th), we have already been approached by 4 independent groups asking for purified protein (2 from academia, 2 from Canadian industry). Our existing platform can be rapidly (within days/weeks) scaled up at BioZone and at SGC to produce all SARS-CoV-2 proteins in larger quantities. The rationale to have both SGC and BioZone involved is to spread the risk between two sites. The risks include ill personnel, building shut-downs, reagent scarcity, and equipment failure. Adhering to open science principles, all our results and materials will be shared without restriction on use.