CRISPR Publication Summary
Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry.
Zhu S, Liu Y, Zhou Z, Zhang Z, Xiao X, Liu Z, Chen A, Dong X, Tian F, Chen S, Xu Y, Wang C, Li Q, Niu X, Pan Q, Du S, Xiao J, Wang J, Wei W
The outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain (NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures.
Science China. Life sciences | 2021-08-20 | PUBMED: 34431042
Supplementary Files:
PMID34431042-Table-S2.xlsx