Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells

During viral entry, enveloped viruses require the fusion of their lipid envelope with host cell membranes. For
coronaviruses, this critical step is governed by the virally-encoded spike (S) protein, a class I viral fusion protein
that has several unique features. Coronavirus entry is unusual in that it is often biphasic in nature, and can occur
at or near the cell surface or in late endosomes. Recent advances in structural, biochemical and molecular
biology of the coronavirus S protein has shed light on the intricacies of coronavirus entry, in particular the
molecular triggers of coronavirus S-mediated membrane fusion. Furthermore, characterization of the coronavirus
fusion peptide (FP), the segment of the fusion protein that inserts to a target lipid bilayer during
membrane fusion, has revealed its particular attributes which imparts some of the unusual properties of the S
protein, such as Ca2+-dependency. These unusual characteristics can explain at least in part the biphasic nature
of coronavirus entry. In this review, using severe acute respiratory syndrome coronavirus (SARS-CoV) as model
virus, we give an overview of advances in research on the coronavirus fusion peptide with an emphasis on its role
and properties within the biological context of host cell entry.