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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2021 ; 12 (1): 961 Nephropedia Template TP
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A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry #MMPMID33574281
Zhu Y; Feng F; Hu G; Wang Y; Yu Y; Zhu Y; Xu W; Cai X; Sun Z; Han W; Ye R; Qu D; Ding Q; Huang X; Chen H; Xu W; Xie Y; Cai Q; Yuan Z; Zhang R
Nat Commun 2021[Feb]; 12 (1): 961 PMID33574281show ga
The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.