Close relatives of new coronavirus variants show varying degrees of virulence

ITHACA, N.
Y.
— As the world enters its third year of pandemic-related uncertainty, one thing seems certain: The SARS-CoV-2 virus has mutated, keeping us on our toes
.

New research from the lab of Gary Whittaker, professor of virology in the College of Veterinary Medicine's Department of Microbiology and Immunology, outlines key messages from the alpha, an older variant of the omicron that emerged in late 2020
.
It turned out that the initial alpha-producing mutation was very similar to the omicron-producing mutation, but the severity of each mutation had very different outcomes

Whitaker is the corresponding author of "Functional evaluation of the proteolytically activated P681H mutation of SARS-CoV-2 variant B.
1.
1.
7 (Alpha) Spike," published Dec.
10 in the journal isscience
.
Other contributors include Susan Daniel, associate professor of chemistry and chemical biology in the College of Arts and Sciences; Diego Diel, associate professor of population medicine and diagnostic sciences (CVM); and postdoctoral fellow Dr.

The scientists noticed a major mutation in a key region of the alpha's spike protein, called the furin cleavage site
.
This place is believed to be the source of the raging virus

However, alpha and ommicron have the same furin-cleaving mutation, which in different genetic backgrounds may explain why ommicron spreads like wildfire but seems to cause less severe disease
.
"Omicron has a lot of the same features as alpha," Whitaker said

Whitaker said Alpha may not be as familiar in the U.

"In the U.
S.
, Alpha didn't get people's attention because it didn't affect us that much at the time," he said
.
"In the UK, it's like a sledgehammer

"When it gets to the U.
S.
," he said, "it's around February (2021), so the impact is much smaller
.
"

Although alpha has no particular impact in the United States, its presence is important from a scientific standpoint
.
This is the first major mutation of the SARS-CoV-2 virus and occurs at the furin cleavage site

While the U.
S.
does feel the severity of the Delta virus, the current Omicron presents something slightly different
.
Emerging evidence suggests that while this latest variant is highly contagious, it is far less harmful

"Omicron is back to square one," Whitaker said
.
"It goes back to the same genetic changes at the alpha protein cleavage site
.
As a disease pathogen, it's a big step back on its evolutionary trajectory
.
"

This was most evident in the variant's ability to cause fusion between cells -- an indication used to determine the virus's ability to cause toxicity in the host
.
"Alpha causes cell fusion," Whitaker said
.
"Delta was going to fuse more cells.
.
.
.
but then came the omicron, whose host cells didn't fuse at all
.
It's gone completely backwards
.
"

If the furin cleavage sites of alpha and omicron are essentially the same, why is alpha a more lethal variant than omicron? The answer must lie in another part of the genetic makeup of these variants, and Whittaker hopes to unravel the mystery
.

At the same time, he said, society has a role to play
.

"The virus will do its own thing, but as a society we have the ability to steer it in one direction or the other through sensible public health policy," he said
.

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