New LANL research shows how COVID infects humans - Albuquerque Journal

New LANL research shows how COVID infects humans

Molecular simulations of the COVID-19 spike protein enable some of the first visualizations of the region of spike that anchors to human host cells. (Courtesy of LANL)

Copyright © 2022 Albuquerque Journal

SANTA FE – New research by two Los Alamos National Laboratory bio-physicists shows how part of the spike protein, those spiky images we have all seen of the virus that causes COVID-19, fuses with and infects human cells.

The research by Karissa Sanbonmatsu and Chang-Shung Tung was presented this week at a meeting of the American Physical Society in Chicago, with about 3,000 physicists and bio-physicists in attendance.

Using the lab’s supercomputers with new computer models to produce molecular simulations has given the researchers some of the first visualizations of that part of the protein spike.

“Developing a digital twin of the extremely tiny, but important, structures allows researchers to explore potential techniques for blocking the infection at the source,” LANL said in a news release.

Researchers have been looking for a clearer understanding of why COVID mutations, such as delta and omicron, can be more contagious or virulent, and why they affect some people and not others, Sanbonmatsu told the Journal in a recent conference call interview.

“This body of work is about the mechanism of how the virus enters the human host cells and specifically how the spike protein enables that, and a lot of the mutations are on the spike protein in omicron and delta,” she said.

Knowing the enemy

LANL public information officer Nancy Ambrosiano, also on the conference call, said, “It really does come down to know your enemy.”

The research is important to “having a clear understanding of the mechanism when you can look at the mutations” and see how things work to “have some ideas about why the different mutants do different things,” she said. “I think it can help us understand future mutations.”

The COVID virus has a unique quality and must pass through a structural change before it can attach itself to and infect human cells, researcher Tung said on the call.

“They (the spike proteins) have a surface protein that helps the virus attach to a human cell, and get into and infect the human cells,” he said. “We have developed a pathway to show how this protein can go from the initial stage to the final stage to invade the human cells.”

Their research has shown that, if you can stop the structural change, perhaps with not yet fully developed drugs, “you can stop the virus (from) invading the human cell,” Tung said.

The two scientists, like many other biophysicists worldwide, have embraced a new technique called cryogenic electron microscopy, or cryo-EM, to image the protein cells to “get the overall architecture of the protein” and then fill in the granular, atomistic details, Sanbonmatsu said.

Imaging advances

Cryo-EM encompasses a broad range of experimental methods, each of which “is based upon the principle of imaging radiation-sensitive specimens in a transmission electron microscope under cryogenic (very low temperature) conditions,” according to the National Institutes of Health website.

In biology, cryo-EM can be used for “imaging intact tissue sections and plunge-frozen cells to individual bacteria, viruses and protein molecules,” according to the website.

Many of the basic structures of the spiky protein were known previously, but because it “has to go through a lot of different transformations, this study really helps work out a lot of those details,” Sanbonmatsu said.

“They (scientists) have to drill ever deeper and deeper into understanding everything about this virus,” Ambrosiano said. “So, using these supercomputers is a way to create imagery that gives new ideas to the innovators in the vaccine world.”

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