Abstract
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.
Keywords: Angiotensin converting enzyme 2 (ACE2); Endocytosis; Phosphoinositides; SARS-CoV-2; Syncytium.
【저자키워드】 SARS-CoV-2, endocytosis, Angiotensin converting enzyme 2 (ACE2), Phosphoinositides, Syncytium., 【초록키워드】 ACE2, COVID-19 pandemic, angiotensin converting enzyme 2, variant, delta variant, angiotensin converting enzyme, viral entry, endocytosis, Spike protein, infections, pseudotype, lentivirus, virus entry, syncytium, cellular entry, cellular, Clathrin-mediated endocytosis, angiotensin, host cells, host cell, causative agent, health emergency, principle, enzyme, human angiotensin converting enzyme 2, treat, cellular receptor, catalytic activity, clathrin, syncytium formation, effective, Cell, intracellular domain, addition, required, dependent on, demonstrated, predominant, entry of SARS-CoV-2, 【제목키워드】 ACE2, host cell, enzymatic activity, domain, required, entry of SARS-CoV-2, PI4KB,