SARS-CoV2 therapeutic discovery through genetic screens and repurposing drugs that target essential virus-host interactions. [Added supplement: COVID-19 Variant Supplement]

The worldwide pandemic of COVID19 caused by the virus SARS-CoV2 has caused over 270,000 human lives and worldwide economic collapse. While public health measures such as social distancing and shutdown of non-essential businesses have been effective at slowing virus spread, restarting society and economies in Canada and around the world will require intensive testing and contract tracing, and ultimately effective treatments and vaccines. In this proposal our goal is identify existing therapeutics that can be re-purposed to treat SARS-CoV2 infections. During an infection viruses must hijack host machinery and regulatory pathways in order to reproduce, and some of the pathways used by viruses are the same ones that are dysregulated during human diseases such as metabolic diseases and cancer. Thus, it is likely that therapeutics designed to treat metabolic diseases and cancer also inhibit SARS-CoV2 infections. However, the specific machinery and regulatory pathways used by SARS-CoV2 remain unknown and the potential inhibitors undiscovered. Our strategy is to identify the host machinery and regulatory pathways the virus needs to grow, and then test drugs that target these proteins to see if they inhibit SARS-CoV. Finally, many different types of coronaviruses likely also use the same host machinery and regulatory pathways so the inhibitors we discover might also be effective against other coronaviruses so could help society prepare for future coronavirus outbreaks and avoid future pandemics.