The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Brian D Quinlan; Huihui Mou; Lizhou Zhang; Yan Gao; Wenhui He; Amrita Ojha; Mark S Parcells; Guangxiang Luo; Wenhui Li; Guocai Zhong; Hyeryun Choe; Michael Farzan

SARS-CoV-2, like SARS-CoV-1, requires expression of the cellular receptor ACE2 to infect cells (Hoffmann et al., 2020; Li et al., 2003; Walls et al., 2020) . ACE2 is a carboxy metalloprotease that, among its other substrates, cleaves angiotensin I (angiotensin 1-10) and angiotensin II (angiotensin 1-8), respectively, to angiotensin (1-9) and angiotensin (1-7). In doing so it counteracts the vasoconstrictive activity of ACE1 (Hamming et al., 2007; Jia, 2016) . Although the catalytic domains of ACE1 and ACE2 are similar, ACE1 inhibitors have no effect on the enzymatic activity ACE2. Moreover, the proteolytic activity of ACE2 does not contribute to SARS-CoV-1 or, presumably, SARS-CoV-2 entry processes (Li et al., 2003) . However interference with ACE2 activity, through S-protein-promoted internalization and degradation, triggered release by cellular proteases, or loss of ACE2-expressing type II pneumocytes, may contribute to SARS and COVID-19 pathology. Although the physiologic role of ACE2 is complex, its activity is described as protective against acute respiratory distress syndrome (ARDS) caused by many agents (Imai et al., 2007) . However administration of soluble recombinant ACE2, although well tolerated, did not attenuate acute lung injury in an early clinical study of ARDS unrelated to COVID-19 (Khan et al., 2017) .