In the G614 variants, you may have 90 percent that are functional. “Because of the shape instability, you may have just 50 percent of them functional. “Say the original virus has 100 spikes,” Chen explains. In the mutant form, the 630 loop (in red) stabilizes the spike, preventing it from flipping open prematurely and making it more functional. Interestingly, the mutated spikes bind more weakly to the ACE receptor, but the fact that they’re less apt to fall apart prematurely renders the virus more infectious overall.Ĭryo-EM structures of the original and mutated SARS-CoV-2 spike protein: The structure of the spike protein in its closed configuration, in its original form (left) and its mutant form (right). “Because the original spike protein would dissociate, it was not good enough to induce a strong neutralizing antibody response,” says Chen.īut when Chen and colleagues imaged the mutant spike protein, they found that the D614G mutation stabilizes the spike by blocking the premature shape change. While this slowed the virus down, the shape change also made it harder for our immune system to contain it. However, as Chen and colleagues reported in 2020, the spikes in the original SARS-CoV-2 sometimes prematurely changed shape and fell apart before the virus could bind to cells. This enables the virus to fuse its membrane with our own cells’ membranes and get inside. They then dramatically change shape, folding in on themselves. To initiate an infection, the spike proteins must bind to the ACE2 receptor. As a result, more functional spikes are available to bind to our cells’ ACE2 receptors, making the virus more infectious. The mutation, they found, makes the spikes more stable than those on the original virus.
Their findings, reported in Science, suggest a straightforward way to improve vaccines.
The D614G mutation alters the genetic code for the SARS-CoV-2 spike protein, which is used in most COVID-19 vaccines, by changing a single amino acid “letter.” To see the effects, Chen and colleagues imaged the spikes with cryo-electron microscopy (cryo-EM), which has resolution down to the atomic level. Adding this change to current vaccines could make them better able to elicit protective neutralizing antibodies.The main circulating SARS-CoV-2 variants (U.K., South Africa, Brazil) all carry a genetic change that stabilizes the spike protein, increasing the chances of infection.
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