Structural impact on SARS-CoV-2 spike protein by D614G substitution (Science)
The fast-spreading UK, South Africa, and Brazil coronavirus variants are raising both concerns and questions about whether COVID-19 vaccines will protect against them. New work led by Bing Chen, PhD, at Boston Children's Hospital analyzed how the structure of the coronavirus spike proteins changes with the D614G mutation -- carried by all three variants -- and showed why these variants are able to spread more quickly. Chen's team imaged the spikes with cryo-electron microscopy (cryo-EM), which has resolution down to the atomic level. They found that the D614G mutation (substitution of in a single amino acid "letter" in the genetic code for the spike protein) makes the spike more stable as compared with the original SARS-CoV-2 virus. As a result, more functional spikes are available to bind to our cells' ACE2 receptors, making the virus more infectious. When Chen and colleagues imaged the mutant spike protein, they found that the D614G mutation stabilizes the spike by blocking the premature shape change. Interestingly, the mutation also makes the spikes bind more weakly to the ACE receptor, but the fact that the spikes are less apt to fall apart prematurely renders the virus overall more infectious.