Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells  

作　　者：Hang Yang Huijun Yuan Xiaohui Zhao Meng Xun Shangrui Guo Nan Wang Bing Liu Hongliang Wang 

机构地区：[1]Department of Pathogen Biology and Immunology,School of Basic Medical Sciences,Xi'an Jiaotong University Health Science Center,Xi'an,710061,China [2]School of Pharmacy,Xi’an Jiaotong University Health Science Center,Xi'an,710061,China [3]BioBank,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710061,China [4]Department of Life Sciences,Faculty of Natural Sciences,Imperial College London,London,SW72AZ,United Kingdom [5]Key Laboratory of Environment and Genes Related to Diseases,Xi'an Jiaotong University,Xi'an,710061,China

出　　处：《Virologica Sinica》2022年第3期380-389,共10页中国病毒学（英文版）

基　　金：supported by the National Natural Science Foundation of China(81871662,82150201);Xi’an Jiaotong University Fund(xzy012019066 and xzy032020037);Xi’an Jiaotong University Health Science Center-Qinnong Bank Fund(QNXJTU-04&QNXJTU-07)。

摘　　要：The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.

关 键 词：SARS-CoV-2 ENDOCYTOSIS PHOSPHOINOSITIDES Angiotensin converting enzyme 2(ACE2) SYNCYTIUM 

分 类 号：R373[医药卫生—病原生物学]