SARS-CoV-2 Variants' Activity in Cells Makes Them More Effective

By Reuters Staff

January 04, 2022

(Reuters) - Along with spike mutations that help the coronavirus break into cells, mutations that change how the virus behaves inside the cells are a big factor in why some variants have been more transmissible, researchers have discovered.

The findings, published in Nature, show that scientists "have to start looking at mutations outside the spike," which has so far been the main focus of vaccines and antibody drugs, said Nevan Krogan of the University of California, San Francisco. Studying the Alpha variant, his team found a mutation at a non-spike site that causes infected cells to ramp up their production of a protein called Orf9B. Orf9b in turn disables a protein called TOM70 that cells use to send signals to the immune system. With higher levels of Orf9B disabling TOM70, the immune system does not respond as well and the virus can better evade detection, the researchers said.

Referring to the increase in Orf9B, Krogan said, "It's rare that mutations 'turn up' a protein. It's a very sneaky thing for this virus to do." The same mutation was identified on Delta, "and sure enough, almost the same mutation is on Omicron," he said, which suggests they may have similar effects on the immune system. The new information could spur development of drugs that target the interaction of Orf9b and TOM70.

SOURCE: https://go.nature.com/3zjmzWR Nature, online December 23, 2021.

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