Harvard Medical School Researchers Identify Covid-19 Mutation That Makes Variants More Contagious

Harvard researchers have identified a mutation in several common Covid-19 variants that causes a structural change in the virus, allowing it to spread more rapidly, according to a study published earlier this month in the journal Science.

The study, which was published on March 16, was conducted by researchers at Boston Children’s Hospital, Harvard Medical School, and Codex BioSolutions, a Maryland-based biotech company.

The researchers focused on the D614G mutation, which mutates exactly one amino acid, or building block, of spike proteins found on the surface of coronavirus variants. These spike proteins are known to be the key mechanism allowing the virus to bind to cells and cause infection.

Bing Chen, the senior author of the paper and a researcher at Boston Children’s Hospital and Harvard Medical School, led a study in July 2020 showing that the spike proteins present on the original strain of Covid-19 were unstable, causing them to dissociate before infecting a cell.

When the coronavirus variants were first identified and reported, researchers hypothesized that the increased infectiousness resulted from an increase in the virus’ binding affinity with the cell receptor. A subsequent study, however, found that the binding affinity of the variant viruses in fact decreased after the mutation.

That mystery, which Chen called “puzzling,” led the Harvard researchers to investigate potential structural differences between the variants and the original virus.

Chen said their study is novel due to its focus on a small feature of the virus.

“Typically, let’s say for a structural biologist, you probably wouldn’t do that because there’s a single residue change. This is a single residue out of 1,273 residues,” Chen said. “Yet, all these observations suggest a large structural difference between these new variants and the original virus.”

Jun Zhang, a research fellow in pediatrics at Boston Children’s Hospital and a member of the research team, said a loop on the variant’s spike proteins increases the virus’s stability, making infection more likely.

Chen’s research lab initially focused on HIV, but when the pandemic started, he and his team switched their focus to the coronavirus. Zhang said his team “wanted to help” Covid-19 research by applying its understanding of HIV, which has a similar spike protein to that of the coronavirus.

Chen said his team's research could have significant implications for the development of future Covid-19 vaccines.

“All these existing vaccines started very early, at an early stage of the pandemic. No one had a choice to pick, so everyone started with the original sequences,” Chen said. “Ideally, what you want would be to combine [the new variants’] changes with this particular variant’s change together to generate the next generation vaccines.”

Chen said current immunity to the coronavirus — whether by vaccination or natural infection — will likely not extend to future variants.

“How resistant they are going to be is always hard to predict,” Chen said. “In the end, you just have to keep incorporating all the changes to fight against these new variants.”