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

Entry of SARS-CoV-2 into ACE2-expressing cells is mediated by its spike (S) protein (Hoffmann et al., 2020; Walls et al., 2020) . The coronavirus S protein is a type I viral entry protein similar to influenza hemagglutinin and the HIV-1 envelope glycoprotein ( Figure 1A and 1B) (Li, 2016) . Like these latter entry proteins, the S protein is processed into two domains, S1 and S2 (Walls et al., 2020) . S1 binds ACE2, whereas S2 anchors the S protein to the viral membrane. The SARS-CoV-2 S protein has an efficient furin cleavage site at its S1/S2 boundary, and this site is processed in virus-producing cells (Coutard et al., 2020) . In contrast, the SARS-CoV-1 S1/S2 junction is cleaved by extracellular or target-cell proteases including TMPRSS2 and cathepsin L (Glowacka et al., 2011; Huang et al., 2006; Millet and Whittaker, 2015) . Both S proteins require processing at a second site, S2', within the S2 domain to mediate fusion of the viral and target cell membranes (Belouzard et al., 2009 ).