The delta variant of SARS-CoV-2 has swept the planet, becoming the dominant variant within just a few months.
In a new study from Boston Children’s Hospital, researchers found why delta spreads so easily and infects people so quickly.
They also suggest a more targeted strategy for developing next-generation COVID-19 vaccines and treatments.
Last spring, the team showed how several earlier SARS-CoV-2 variants (alpha, beta, G614) became more infectious than the original virus.
Each variant acquired a genetic change that stabilized the spike protein on the virus’s surface, the protein on which current vaccines are based.
But the delta variant, which emerged soon after, is the most infectious variant known to date.
Using two kinds of cell-based assays, the team demonstrated that delta’s spike protein is especially adept at membrane fusion.
This allowed a simulated delta virus to infect human cells much more quickly and efficiently than the other five SARS-CoV-2 variants.
Delta had the advantage especially when cells had relatively low amounts of the ACE2 receptor.
The team also investigated how mutations in the variants affect the spike protein’s structure.
They imaged spike proteins from the delta, kappa, and gamma variants, and compared them to spikes from the previously characterized G614, alpha, and beta variants.
All six variants showed changes in two key parts of the spike protein that our immune system recognizes: the receptor-binding domain (RBD), which binds to the ACE2 receptor, and the N-terminal domain (NTD).
The first thing the team noticed about delta was that there was a large change in the NTD, which is responsible for its resistance to neutralizing antibodies.
The RBD also changed, but this led to little change in antibody resistance. Delta still remained sensitive to all the RBD-targeted antibodies that we tested.
The researchers believe that the RBD is a more favorable target for the next generation of vaccines and antibody treatments.
The study is published in Science. One author of the study is Bing Chen, Ph.D.
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