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

• DOI: 10.1016/j.virs.2022.03.003
• Publication Date: 2022-03-07T21:41:23Z
• Authors: Hang Yang; Huijun Yuan; Xiaohui Zhao; Meng Xun; Shangrui Guo; Nan Wang; Bing Liu; Hongliang Wang
• Keywords: Syncytium

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, using lentivirus based pseudotypes bearing protein, we demonstrated that into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, showed intracellular domain catalytic activity ACE2 were not required for efficient virus entry. Finally, current predominant Delta variant, although high infectivity syncytium formation, also entered through endocytosis. These results provide new insights present proof principle targeting viral could be an effective way to treat different variant infections.