SARS-CoV
High zoonotic potential
(Kaoru Whittaker 2014 pmid: 25445340) -
Corona and Protein S
(Simmons Pöhlmann 2011 Virology - pmid: 21435673) Coronaviruses, including SARS-CoV, harbour three envelope proteins, spike (S), membrane (M), and envelope (E), which are required for virion assembly, release and infectious entry into target cells (Masters, 2006). The SARS-CoV-S-protein (SARS-S) mediates infectious cellular entry (Hofmann et al., 2004b; Simmons et al., 2003; Yang et al., 2004) and constitutes the major target of the neutralizing antibody response (Hofmann and Pöhlmann, 2004; Nie et al., 2004b, 2004a). The carboxypeptidase angiotensin-converting enzyme 2 (ACE2) is used by SARS-CoV as receptor for cell entry (Li et al., 2003; Wang et al., 2004) and is expressed on type II pneumocytes, the major viral target cells (Hamming et al., 2004; Mossel et al., 2008; To et al., 2004). Several cellular C-type lectins augment or facilitate SARS-S-driven entry (Gramberg et al., 2005; Jeffers et al., 2004; Marzi et al., 2004; Yang et al., 2004). However, ACE2 but not C-type lectin expression correlates with susceptibility to SARS-S-driven infection (Hofmann et al., 2004a; Nie et al., 2004b) and is essential for SARSCoV spread in experimentally infected mice (Kuba et al., 2005), indicating that ACE2 is a major and likely the only receptor used by SARS-CoV in the infected host. Collectively, SARS-S interacts with host cell factors to mediate the first essential step in the viral life cycle, virus entry into target cells, and constitutes an attractive target for preventive and therapeutic approaches.
Spike host cell receptor interactions
(Kaoru Whittaker 2014 pmid: 25445340) - While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin.