Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

Eric W. Stawiski; Devan Diwanji; Kushal Suryamohan; Ravi Gupta; Frederic A. Fellouse; J. Fah Sathirapongsasuti; Jiang Liu; Ying-Ping Jiang; Aakrosh Ratan; Monika Mis; Devi Santhosh; Sneha Somasekar; Sangeetha Mohan; Sameer Phalke; Boney Kuriakose; Aju Antony; Jagath R. Junutula; Stephan C. Schuster; Natalia Jura; Somasekar Seshagiri

As with SARS-CoV and a related alpha-coronavirus NL63 (HCoV-NL63), SARS-CoV-2 employs the human ACE2 cell surface protein as a receptor to gain entry into cells (Hoffmann et al., 2020; Letko et al., 2020; Lin et al., 2008; Ou et al., 2020; Zhou et al., 2020a) . The virus surface spike glycoprotein (S-protein) constitutes a key determinant of viral host range and contains two domains, S1 and S2, which are separated by a protease cleavage site (Li, 2016) . A successful host cell invasion by the virus involves direct binding of the virus S1 receptor binding domain (RBD) to the host ACE2 peptidase extracellular domain (PD), exposing the S1-S2 interdomain protease site that upon cleavage by host proteases leads to S2-mediated virus-4 host cell membrane fusion (Belouzard et al., 2009; Hoffmann et al., 2020; Li, 2016; Li et al., 2005a; Simmons et al., 2005) .