SARS-CoV-2 gains entry to host cells via angiotensin-converting enzyme 2 (ACE2). Now, research demonstrates a role for a soluble form of ACE2 (sACE2) and vasopressin in mediating SARS-CoV-2 entry into susceptible cells. Using kidney HK-2 cells, which are highly susceptible to SARS-CoV-2 infection, Yeung et al. show that interaction of the SARS-CoV-2spike protein with sACE2 or with a complex of sACE2 plus vasopressin mediates receptor-mediated endocytosis of the virus via type 1 angiotensin and vasopressin V1b receptors, respectively.