Researchers have created the first 3D atomic scale map of the part of the 2019 coronavirus 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 a vaccine and antiviral drugs to combat the coronavirus.
The researchers are also working on a related viable vaccine candidate stemming from the research.
The researchers 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,” says Jason McLellan, an associate professor at the University of Texas at Austin who led the research, “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.”
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 write a paper on the work. The many steps involved in this process would typically take months to accomplish.
State-of-the-art technology known as cryogenic electron microscopy (cryo-EM) was key to the success. Cryo-EM allows researchers to make atomic-scale 3D models of cellular structures, molecules, and viruses.
The molecule the team produced, and for which they obtained a structure, represents only the extracellular portion of the spike protein. It’s enough, however, 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 coronavirus vaccine to take effect.
The paper appears in the journal Science.
Additional coauthors are from the NIH’s Vaccine Research Center in Bethesda, Maryland and UT Austin. Coauthors Nianshuang Wang, Kizzmekia Corbett, Barney Graham, and McLellan are inventors on a US patent application for the structure of coronavirus spike proteins in the prefusion conformation and their use in therapeutics. Coauthors Daniel Wrapp, Wang, Corbett, Olubukola Abiona, Graham, and McLellan are inventors on a US patent application for the vaccine candidate.
Support for this work came, in part, from the National Institutes of Health and the National Institute of Allergy and Infectious Diseases.
Source: University of Texas at Austin
