“Surfaceome CRISPR screening for SARS-CoV-2 virulent proteins”
COBRE for Computational Biology of Human Disease
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19). SARS-CoV-2 produces not only structural viral proteins but also non-structural accessory proteins into extracellular space in COVID patients. Accumulation of these proteins is associated with pathogenic outcomes of COVID, and considered as a potential contributor of cytokine storm, although their cellular receptor and the mechanisms of these phenomena remain elusive.
We generated a focused CRISPR activation (CRISPRa) library, named surfaceome, that covers all ~6000 known/predicted surface proteins on the cellular plasma membrane. We leveraged the screening platform to identify cellular receptors for secreted virulence proteins of SARS-CoV-2, Orf3a, Orf7a, and Orf8 and identified cellular receptors for the virulent viral proteins.
This research is supported by R00 AI141683 (S.L.), P20 GM109035 (S.L.), the Smith Family Awards Program for Excellence in Biomedical Research (S.L.), the Charles H. Hood Foundation Child Health Research Award (S.L.)