Development of a SARS-CoV-2 spike protein binding assay using human epithelial cells for COVID-19 therapy discovery and development

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The urgency of the current COVID-19 pandemic needs new treatments to be developed as quickly and as safely as possible. Whatever comes out of the many labs involved in these efforts needs to be tested in a variety of ways to help us know if they will work when given to people who might be infected by SARS-CoV-2, the virus which causes COVID-19\. For the virus to cause this disease, it needs to get inside some of our cells where it can survive, multiply and then infect other cells in the body. To do this, the virus first needs to latch onto our cells. For this, it uses a specific part on the outside of the virus, the 'spike', to fasten onto special parts on the outside of our cells ('receptors') to which if fits, like a key fits a lock.This project will recapitulate this first essential step of viral infection allowing us to test new treatments 'in a dish' in order to support the therapeutic discovery effort against COVID-19\. Whilst models to support this development are available using systems with purified components of cells (using the 'receptors' the virus uses for entry), or, using the intact virus, there is a lack of cellular models that can be used in a simple manner for testing the impact of drugs, and antibodies arising from vaccination, on specific steps of viral entry into human cells. We intend to develop a 'cell-based' model using human cells (including cells lining the lung, which are known to be a key site of entry for the virus) and SARS-CoV-2 purified spike protein. This biological model will enable us and our industrial partners to test their therapeutics on a very specific step vital for viral infection. We will use advanced imaging techniques to visualise this binding of the viral spike protein to human cells, and, we will then be able to test how drugs, or other agents such as antibodies generated by a vaccine, impact this specific step of viral entry. This will then enable candidate drugs to be selected as therapeutics, improved versions of drugs to be developed or support the selection of vaccines that generate protective antibodies against the virus.