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Coronavirus breakthrough: First 3D protein map paves way for vaccine design

State-of-the-art microscopy has enabled researchers to study a viral protein that could be used in vaccine development.

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A transmission electron microscope captured this image of the SARS-CoV-2 coronavirus, which has a distinctive crown-like appearance.

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The first 3D map of SARS-CoV-2, the coronavirus responsible for over 2,000 deaths since December 2019, has been produced by a collaboration of coronavirus researchers at the University of Texas at Austin and the National Institutes of Health. Heralded as a breakthrough, the map provides a stepping stone to the development of antivirals or vaccines to stymie the virus.

In under two months, infections of the novel coronavirus have soared past 75,000 and caused significant economic turmoil in China and abroad. The World Health Organization has declared the outbreak a public health emergency of international concern and when it announced the name of the disease on Feb. 11, it added that a vaccine was likely 18 months away.

But scientists are mobilizing their resources quickly, sharing information about the virus with unprecedented pace, and turning experiments into peer-reviewed research in a matter of weeks.

That's the case for Jason McLellan, a structural biochemist, and his team at UT Austin who have been studying similar coronaviruses for years. Their latest study, published in the journal Science on Wednesday, took advantage of state-of-the-art technology at the university to map the molecular structure of the novel coronavirus, with a particular focus on the virus' "spike protein." 

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The molecular structure of the spike protein.

Jason McLellan/Univ. of Texas at Austin

The protein is critical to the survival of the virus because it enables it to get inside human cells and begin making copies of itself. However, what makes it dangerous also makes it a target.

The chief function of a vaccine is to prime the immune system. They work by presenting small parts of harmful pathogens like viruses and bacteria to our army of immune cells. It's like a molecular "WANTED!" poster -- the immune system gets a good look at any nasty bugs and starts to keep watch. If the real virus or bacteria sneak into the body, the immune system is ready and sends out an army of cells and antibodies to stop the invader. The spike protein can act as the wanted poster.

After Chinese researchers shared the genetic sequence of the virus in January, the team were able to design and produce samples of the spike protein in the lab. Using a specialized form of microscopy, they then mapped its structure.

The research team showed there are similarities between the spike protein in the coronavirus responsible for the 2002-2003 SARS outbreak and the new coronavirus, SARS-CoV-2. However, the latter appears to bind to human cells much more strongly than the SARS virus did and antibodies against the first SARS virus don't seem to react to the new virus in the same way.

Creating the 3D map of the spike protein in SARS-CoV-2 is the first step in speeding up vaccine design and development, but experiments to examine how successfully it elicits an immune response are ongoing, according to McLellan, but looking to previous viruses provides a little hope.

"The spike proteins from other coronaviruses, such as MERS-CoV and SARS-CoV have been very immunogenic when used as a vaccine antigen," McLellan says. "We expect the same to be true for this novel coronavirus." 

Originally published Feb. 19, 7:15 a.m. PT.
Update, 2 p.m.: Clarifies work in immunogenicity, adds link to paper in Science.