Surfaceome CRISPR Screening for SARS-CoV-2 Virulent Proteins

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19). Spike protein is the primary antigenic target for COVID vaccines and interfering with the interface between RBD (Receptor Binding Domain) of spike and ACE2 is the mechanism of action for the majority of existing therapeutic antibodies, indicating the importance of RBD and its binding to the cellular receptor for controlling SARS-CoV-2. It is unclear whether there are any intrinsic cellular proteins that inhibit viral entry of SARS-CoV-2.

We will leverage the screening platform to identify cellular receptors for secreted virulence proteins of SARS-CoV-2, Orf3a, Orf7a, and Orf8. Importantly, the same screening platform is validated to be a efficient platform for secreted virulent proteins. In a separate screening for norovirus secreted virulence protein (NS1), the surfaceome screening successfully identified Syndecan-4 as a putative cellular receptor for norovirus NS1 (Li et al., In preparation). In the Aim 2, we will perform a surfaceome screening for Orf3a, Orf7a, and Orf8 and will discover putative cellular receptors for the secreted virulence proteins.