Connections between biomechanics and higher infectivity: a tale of the D614G mutation in the SARS-CoV-2 spike protein

摘要

The structure and infectivity of the wild-type (D614) and mutant (D614G) spike proteins. a An illustration of SARS-CoV-2 infecting human lungs. b Cryo-EM structure of the spike proteins (PDB: 6vsb and 6xs6), the black circle in the center indicates the position of the amino acid D614 and/or D614G. The structures of the wild-type (cyan) and mutant (red) spike proteins were superimposed, which show an overall similar architecture between them with an rmsd of 0.77 Å. The first inset (upper panel) shows residues D614 in cyan and D614G in red. The second inset (lower panel) shows residue D614 forming an H-bond with T859 of the adjacent protomer in the wild-type spike protein (PDB: 6vsb). The D614G mutation causes an increase in the distance between D614G and T859, which results in elimination of the H-bond formation between them (PDB: 6XS6). c An illustration of mutant SARS-CoV-2 infecting human lungs. d The D614G spike trimer is comparatively more flexible and adopts at least four major conformations in contrast to two observed for the D614 protein trimer. The D614G mutation causes spike protein trimer to occupy more open conformations, which increases the probability of ACE2 receptor binding and the virion membrane-target cell fusion. Circles in light green indicate close conformation of the protomer and illustrations of Pac-Man in the dark green indicate open conformation of the protomer. The figures were prepared using Pymol and Adobe Illustrator