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Breakthrough in coronavirus research results in new map to support vaccine design

February 19, 2020

Science Daily/University of Texas at Austin

Researchers have made a critical breakthrough toward developing a vaccine for the 2019 novel coronavirus by creating the first 3D atomic scale map of the part of the virus that attaches to and infects human cells. Mapping this part, called the spike protein, is an essential step so researchers around the world can develop vaccines and antiviral drugs to combat the virus.

Mapping this part, called the spike protein, is an essential step so researchers around the world can develop vaccines and antiviral drugs to combat the virus. The paper is publishing Wednesday, Feb. 19 in the journal Science.

The scientific team is also working on a related viable vaccine candidate stemming from the research.

Jason McLellan, associate professor at UT Austin who led the research, and his colleagues have spent many years studying other coronaviruses, including SARS-CoV and MERS-CoV. They had already developed methods for locking coronavirus spike proteins into a shape that made them easier to analyze and could effectively turn them into candidates for vaccines. This experience gave them an advantage over other research teams studying the novel virus.

"As soon as we knew this was a coronavirus, we felt we had to jump at it," McLellan said, "because we could be one of the first ones to get this structure. We knew exactly what mutations to put into this, because we've already shown these mutations work for a bunch of other coronaviruses."

The bulk of the research was carried out by the study's co-first authors, Ph.D. student Daniel Wrapp and research associate Nianshuang Wang, both at UT Austin.

Just two weeks after receiving the genome sequence of the virus from Chinese researchers, the team had designed and produced samples of their stabilized spike protein. It took about 12 more days to reconstruct the 3D atomic scale map, called a molecular structure, of the spike protein and submit a manuscript to Science, which expedited its peer review process. The many steps involved in this process would typically take months to accomplish.

Critical to the success was state-of-the-art technology known as cryogenic electron microscopy (cryo-EM) in UT Austin's new Sauer Laboratory for Structural Biology. Cryo-EM allows researchers to make atomic-scale 3D models of cellular structures, molecules and viruses.

"We ended up being the first ones in part due to the infrastructure at the Sauer Lab," McLellan said. "It highlights the importance of funding basic research facilities."

The molecule the team produced, and for which they obtained a structure, represents only the extracellular portion of the spike protein, but it is enough to elicit an immune response in people, and thus serve as a vaccine.

Next, McLellan's team plans to use their molecule to pursue another line of attack against the virus that causes COVID-19, using the molecule as a "probe" to isolate naturally produced antibodies from patients who have been infected with the novel coronavirus and successfully recovered. In large enough quantities, these antibodies could help treat a coronavirus infection soon after exposure. For example, the antibodies could protect soldiers or health care workers sent into an area with high infection rates on too short notice for the immunity from a vaccine to take effect.

https://www.sciencedaily.com/releases/2020/02/200219152850.htm

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Coronavirus Larry Minikes Coronavirus Larry Minikes

COVID-19 a reminder of the challenge of emerging infectious diseases

February 28, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC). Their commentary appears in The New England Journal of Medicine.

NIAID Director Anthony S. Fauci, M.D., NIAID Deputy Director for Clinical Research and Special Projects H. Clifford Lane, M.D., and CDC Director Robert R. Redfield, M.D., shared their observations in the context of a recently published report on the early transmission dynamics of COVID-19. The report provided detailed clinical and epidemiological information about the first 425 cases to arise in Wuhan, Hubei Province, China.

In response to the outbreak, the United States and other countries instituted temporary travel restrictions, which may have slowed the spread of COVID-19 somewhat, the authors note. However, given the apparent efficiency of virus transmission, everyone should be prepared for COVID-19 to gain a foothold throughout the world, including in the United States, they add. If the disease begins to spread in U.S. communities, containment may no longer be a realistic goal and response efforts likely will need to transition to various mitigation strategies, which could include isolating ill people at home, closing schools and encouraging telework, the officials write.

Drs. Fauci, Lane and Redfield point to the many research efforts now underway to address COVID-19. These include numerous vaccine candidates proceeding toward early-stage clinical trials as well as clinical trials already underway to test candidate therapeutics, including an NIAID-sponsored trial of the experimental antiviral drug remdesivir that began enrolling participants on February 21, 2020.

"The COVID-19 outbreak is a stark reminder of the ongoing challenge of emerging and re-emerging infectious pathogens and the need for constant surveillance, prompt diagnosis and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures," the authors conclude.

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Materials provided by NIH/National Institute of Allergy and Infectious DiseasesNote: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/02/200228142016.htm

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