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Unraveling the mysterious mutations that make delta the most transmissible COVID virus yet

Liz Szabo, Kaiser Health News on

Published in News & Features

The P681R mutation, also found in the kappa variant, is located at the beginning of a part of the genome called the furin cleavage site, Cooper said.

Furin is a naturally occurring human enzyme that gets hijacked by the coronavirus, which uses it to slice the spike protein into the optimal shape for entering the cell, Rasmussen said. The new mutation makes that sculpting more efficient, Rasmussen said.

Another delta mutation — also found in kappa and epsilon — is called L452R. Experiments suggest this mutation, which also affects the receptor-binding domain, acts to prevent antibodies from neutralizing the virus, Cooper said.

These mutations appear to be more formidable as a team than alone.

The genetic changes “are certainly doing something, but why that combination makes the delta variant more fit is not entirely obvious,” Bedford said. “Putting them together seems to matter.”

Delta also has developed genetic changes not seen in other variants.


One such spike mutation is called D950N. “This might be unique,” Cooper said. “We don’t see that anywhere else.”

The D950N mutation is different than other mutations because it’s located outside the receptor-binding domain in an area of the coronavirus genome that helps the virus fuse with human cells, Cooper said. Fusing with human cells allows the coronavirus to dump its genetic material into those cells.

This mutation could affect which types of cells the virus infects, potentially allowing it to harm different organs and tissues. Mutations in this region are also associated with higher viral loads, Cooper said.

Delta also contains mutations in a part of the spike protein called the N-terminal domain, which provides a “supersite” for antibodies to latch onto the virus and prevent it from entering cells, said Dr. Hana Akselrod, an infectious diseases specialist at the George Washington University School of Medicine & Health Sciences.


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