Ultrapotent and broadly neutralizing engineered biologics as therapeutics for SARS-CoV-2

The COVID-19 pandemic is caused by an infection with the SARS-CoV-2 virus. Antiviral antibodies targeting this virus can block its ability to infect individuals, and thus, they are a promising treatment. Though natural antibodies derived from infected individuals are a common source of antiviral antibodies, they are limited in their ability to resist viral mutations and have consequently been rendered ineffective as the pandemic has dragged on and viral variants have emerged. In contrast, advanced antibody engineering technologies enable these limitations to be overcome without increasing costs. Leveraging our expertise in antibody engineering, we have generated antibodies targeting multiple sites on the SARS-CoV-2 virus that are essential for entry of the virus into cells, and we have shown that treatment of cellular and animal models of infection with these antibodies can reduce infection. In this project, we propose to further engineer these antibodies to enhance their efficacy and ensure that they remain effective against emerging variants of the virus. To achieve this, the antibodies will be optimized to potently neutralize viral infections, including those arising from both existing and future variants of concern. We will then test the antibodies in cellular and animal models of infection to gauge their efficacy in direct comparison with clinically authorized antibodies, to validate the superiority of our approach. Overall, we aim to create an effective anti-COVID19 therapeutic drug candidate that will remain effective against diverse versions of the virus, to provide a direly needed treatment for infected patients. These new antivirals should help reduce the burdens on health, economy and society that the pandemic has imposed on Canada and the world.