Human Coronavirus Spike

Spike Protein Overview

The Coronavirus Spike protein is a class I viral fusion protein and mediates attachment to the host receptor. The size of the abundantly N-glycosylated S protein varies greatly between CoV species ranging from approximately 1100 to 1600 residues in length, with an estimated molecular mass of up to 220 kDa. Trimers of the S protein form the 18–23-nm long, club-shaped spikes that decorate the membrane surface of the CoV particle. The spike protein is the common target for neutralizing antibodies and vaccines.

The Spike protein can be divided into two functionally distinct subunits: the globular S1 subunit is involved in receptor recognition, whereas the S2 subunit facilitates membrane fusion and anchors S into the viral membrane. S1 makes up the large receptor-binding domain of the S protein while S2 forms the stalk of the spike molecule.

The S1 subunit of the betacoronavirus spike proteins displays a multidomain architecture and is structurally organized in four distinct domains A–D of which domains A and B may serve as a RBD. The S2 subunit is highly conserved which contains the key protein segments that facilitate virus-cell fusion. These include the fusion peptide, two heptad repeat regions (HR1 and HR2) and the transmembrane domains which are well conserved among CoV species across different genera. The S gene of SARS-CoV-2 was highly divergent to other CoVs , with less than 75% nt sequence identity to other SARSr-CoVs except a 93.1% nt identity to RaTG13. The major differences in 2019-nCoV are the three short insertions in the N-terminal domain, which may confer to sialic acid binding activity, and four out of five key residues changes in the receptor-binding motif, in comparison with SARS-CoV.

Spike- Receptor Interaction

Studies of coroanvirus spike glycoprotein showed that both the N-terminal region (NTR, domain A in β-CoV) and the C-terminal region of S1 (CTR, comprising domain B, C, and D in β-CoV) can bind host receptors and hence function as RBDs . The CTR of alpha- and betacoronaviruses appears to bind proteinaceous receptors exclusively.
(Ref: R.J.G. Hulswit.Coronavirus Spike Protein and Tropism Changes.Advances in Virus Research. 2016)