Host cellular protein substrates of SARS-CoV-2 proteases [Added supplements: Sex as biological variable supplement, COVID-19 Variant Supplement]

The recent outbreak of coronavirus SARS-CoV-2 (2019-2020) leading to COVID-19 disease in China and worldwide has led to increased urgency in identifying strategies to mitigate the spread of coronavirus infection and treat infected individuals. No established treatments exist, thus there is a need to identify antiviral targets. As evidenced of recurring SARS-CoV (2003) and MERS-CoV (2012) outbreaks, there is also a need for long-term preparations to counteract future emerging coronavirus outbreaks. Currently, the pathogenic mechanisms that lead to COVID-19 and related SARS/MERS-CoV diseases are not understood. In this study, we will identify the host proteins that are targeted by a viral protein called a protease using an unbiased proteomics approach. Identifying the protein targets of SARS/MERS-CoV proteases will reveal into the protein sequence that binds to the proteases. We will engineer and optimize decoy protein sequences that will effectively block SARS/MERS-CoV protease function and thus, inhibit SARS/MERS-CoV infection. Uncovering the proteins that are targeted by the SARS/MERS-CoV proteases will also provide a catalog of the host processes that these viruses affect, thus gaining insights into the pathogenic mechanisms that lead to COVID-19 disease.