Researchers from The University of Texas at Austin and the NIH have created the first 3D atomic scale map of the part of the 2019 novel coronavirus that attaches to and infects human cells. Mapping this part, called the spike protein, is an essential step toward the development of vaccines and antiviral drugs to combat the virus.
Jason McLellan, senior author on a paper published in Science today, 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."
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. 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.
Image: A 3D atomic scale map, or molecular structure, of the 2019-nCoV spike protein. The protein takes on two different shapes, called conformations—one before it infects a host cell, and another during infection. This structure represents the protein before it infects a cell, called the prefusion conformation. Image courtesy of Jason McLellan/Univ. of Texas at Austin.