A genome-wide RNAi screening using a human kidney cell line HM-2 that is highly susceptible to SARS-CoV-2 identified that the soluble ACE2 (sACE2) supports SARS-CoV-2 infection in culture cells. The S protein of virion surface interacts with sACE2, and SARS-CoV-2 enters to the target cells through endocytosis, which is triggered by the interaction of cellular receptor AT1 with virus-bound sACE2. sACE2 is physiologically interacts with vasopressin. This sACE2 and vasopressin complex can also associate with S protein, in that case, viruses enters the target cells via a vasopressin receptor AVPR1B. This study proposes alternative strategies of SARS-CoV-2 cell entry that do not require the interaction between S protein and cell surface ACE2.
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