Spike-host interactions - SARS-CoV

Role of the spike in cell entry

(Kaoru Whittaker 2014 pmid: 25445340) - The success of coronaviruses in their ability to jump between species may be attributed, in part, to the diverse array of virus entry strategies they deploy to infect target cells (Belouzard et al., 2012; Bosch and Rottier, 2008). Coronavirus entry is largely controlled by the spike surface envelope glycoprotein (S) since it bears both receptor binding and membrane fusion capabilities (Masters and Perlman, 2013). As such, the S glycoprotein is a crucial determinant of tissue and cell tropism as well as host range. Coronaviruses are notable because at each step of virus entry, which includes receptor binding, activation of fusion, and internalization, a multitude of mechanisms and strategies have evolved (Belouzard et al., 2012). For example, depending on the coronavirus species, the S protein can mediate binding to a proteinaceous receptor or to carbohydrate moieties.

Entry mechanism

(Kaoru Whittaker 2014 pmid: 25445340) - Coronaviruses can enter cells via fusion either directly at the cell surface or can be internalized through the endosomal compartment. The mouse hepatitis virus (MHV) is a prime example of the flexibility in entry mechanisms used. A variant of the MHV-4 strain was shown to be able to fuse directly at the cell surface at neutral pH and also enter cells through an endocytic route (Nash and Buchmeier, 1997), whilst the MHV-2 strain enters cells through endocytosis by a clathrin-dependent mechanism (Pu and Zhang, 2008; Qiu et al., 2006). Importantly, coronaviruses employ a diversity of cues, such as receptor binding, low pH and proteolytic activation, to activate the S protein, allowing a timely release of the fusion peptide into target membranes (Bosch and Rottier, 2008). This enables a spatiotemporally controlled orchestration of viral entry steps.

proteolytic activation

(Kaoru Whittaker 2014 pmid: 25445340) - The S protein is often activated for fusion by means of proteolytic processing by host cell proteases, an activation process that is typical of class I viral fusion proteins (White et al., 2008). Remarkably, for some coronaviruses, such as SARS-CoV, cleavage of S can occur at two distinct sites (Belouzard et al., 2009). A variety of proteases have been shown to mediate coronavirus activation (Belouzard et al., 2012).

(Walls Veesler 2020 Cell - pmid: 32155444) - SARS-CoV-2 see: S protein - SARS-CoV-2