"a, The density map for the bat virus trimeric S is shown, with the long axis vertical in the top panel and in an orthogonal view in the bottom panel. All of the particles are in the closed conformation, likely because of the cross-linking of the material. The three monomers are colored blue, yellow and brown. 
b, Molecular model of the bat virus S protein, colored as in a, with substitutions between the bat virus and SARS-CoV-2 highlighted. Most of the changes are in the RBD and are colored red; there are four substitutions in S1 outside of the RBD, which are shown in green, and a single substitution in S2 is shown in blue.
c, Overlay of the molecular structure of a portion of the RBD–RBD interface; the two bat virus S monomers are colored gold (top) and pink (bottom), and the two superposed SARS-CoV-2 S RBD chains are shown in green (top) and blue (bottom). Analysis suggests that the residues at the interface of SARS-CoV-2 S RBD chains support several additional stabilizing interactions and avoid the potential steric repulsion between His505 and His440, seen in the structure of the bat virus. 
d, The density map for the uncleaved SARS-CoV-2 S protein, in the closed conformation, shown in the same orientation as in a, with the subunits colored blue, green and yellow. This sample gave the best quality maps and enabled the most extensive build of the polypeptide chain."

Fig. 2: Structural comparison of the S glycoproteins from the bat virus RaTG13 and from SARS-CoV-2

Cry-electron microscopy (cryo-EM) structures of S glycoprotein of bat virus RaTG13 and an uncleaved SARS-CoV-2 were created. The structure of the S glycoprotein in RaTG13 is shown to be very similar to that of the closed form of uncleaved SARS-CoV-2.

University of Michigan - Ann Arbor

- Cry-electron microscopy (cryo-EM) structures of S glycoprotein of bat virus RaTG13 and uncleaved SARS-CoV-2
- S glycoprotein sequences of RaTG13 and SARS-CoV-2
- S glycoprotein stability 
- Bat virus RaTG13 and SARS-CoV-2 S glycoprotein affinities to human receptor ACE2

Comparison of S glycoprotein between RaTG13 and uncleaved SARS-CoV-2

Wrobel, A.G., Benton, D.J., Xu, P. et al. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat Struct Mol Biol (2020). https://doi.org/10.1038/s41594-020-0468-7

SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects

Cry-electron microscopy (cryo-EM) structures of S glycoprotein of bat virus RaTG13 and uncleaved SARS-CoV-2

The S protein sequences of both the RaTG13 and SARS-CoV-2 were 97.8% conservative in the ectodomain. However, 89.6% of the sequence in the receptor-binding domain (RBD) varied, with substitutions in the ACE2-receptor-binding surface and the RBD–RBD interfaces of the trimeric S.

S glycoprotein sequences of RaTG13 and SARS-CoV-2

Using thermal-stability data, it was concluded that the uncleaved SARS-CoV-2 S protein had higher stability than RaTG13 S protein and cleaved SARS-CoV-2 had similar stability to uncleaved RaTG13 protein. 

S glycoprotein stability

Amplitude analysis provides evidence that SARS-CoV-2 binds more tightly to human ACE2 than the bat virus protein does by around 1,000 times. 

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