Attachment Factor and Receptor Engagement of Sars Coronavirus and Human Coronavirus NL63

The cellular membrane constitutes a physical barrier against viral infection. Enveloped viruses developed specialized proteins to overcome this barrier. These proteins, which are often extensively glycosylated, are inserted into the viral membrane and mediate both recognition of target cells and fusion of the viral membrane with a host cell membrane. The latter process allows introduction of the viral genome and associated viral proteins into the host cell lumen and is therefore critical for establishment of productive infection. which in the case of coronaviruses (CoV) are termed spike (S) proteins, are attractive targets for inhibitors and vaccines. Enveloped viruses evolved two prototypes of glycoproteins to enter target cells, termed class I and class II fusion proteins. 4 Class I fusion proteins are found in, e.g., retroviruses and paramyxoviruses, while, e.g., flaviviruses and alphaviruses encode class II fusion proteins. Both types of fusion proteins exhibit a distinct functional organization, which is reflected by their different spatial orientations. Thus, class I fusion proteins are oriented perpendicular to the cellular membrane and are visible as spikes in electron micrographs, while class II proteins are oriented horizontally relative to the cellular membrane and are well ordered on the virion surface. Viral class I fusion proteins are organized into a globular surface unit (SU), which interacts with cellular receptors, and a transmembrane unit (TM), which harbors highly conserved sequence elements required for membrane fusion. Membrane fusion is initiated by binding of SU to cellular receptor(s) or by exposure of the glycoprotein to low pH, which triggers conformational changes in the glycoprotein that activate TM. TM-driven membrane fusion is initiated by insertion of a N-terminal fusion peptide into the target cell membrane, followed by