Scientists produce a 3D map of the spike protein of SARS-CoV-2, researchers have made a breakthrough to develop a vaccine against the coronavirus of SARS-COV-2.
Researchers have made a breakthrough towards the development of a vaccine for the SARS-CoV-2 coronavirus, also known as 2019-nCoV, by creating the first atomic scale 3D map of its spike protein, part of a virus that binds and infects human cells.
This transmission electron microscope image shows SARS-CoV-2, also known as 2019-nCoV, the virus that causes COVID-19, isolated from a patient in the U.S. UU., Which emerges from the surface of cells grown in the laboratory. Image of NIAID-RML.
“The new coronavirus has recently emerged as a human pathogen in the city of Wuhan, in the Chinese province of Hubei, causing fever, severe respiratory diseases and pneumonia, a disease recently called COVID-19,” said lead author Dr. Jason McLellan, of the Department of Molecular Biosciences at the University of Texas at Austin and colleagues.
“The emerging pathogen was quickly characterized as a novel member of the betacoronavirus genus, closely related to several bat coronaviruses, as well as to SARS-CoV.” Compared to the SARS-CoV, the SARS-CoV-2 seems to be transmitted more easily from person to person, extending to multiple continents.
“It makes use of a densely glycosylated spike protein to enter host cells.” Dr. McLellan’s team had already developed methods to block spike proteins in other coronaviruses, including SARS-CoV and MERS-CoV, in a way that made them easier to analyze and could effectively turn them into vaccine candidates.
This experience gave them an advantage over other research teams studying the new virus. “As soon as we learned that it was a coronavirus, we felt we had to jump on it, because we could be one of the first to get this structure,” said Dr. McLellan.
“We knew exactly what mutations to put into this, because we have already shown that these mutations work for many other coronaviruses.”
(A) scheme of the primary structure of the spike protein, colored by domain; the domains that were excluded from the ectodomain expression construct or that could not be visualized on the final map are white. Abbreviations: SS – signal sequence, NTD – N-terminal domain, RBD – receptor binding domain, SD1 – subdomain 1, SD2 – subdomain 2, S1 / S2 – protease cleavage site S1 / S2, cleavage site of S2′-S2 ‘protease, FP-fusion peptide, HR1-heptad repeat 1, CH-central helix, CD-linker domain, HR2-heptad repeat 2, TM-transmembrane domain, CT-cytoplasmic tail; the arrows denote protease cleavage sites;
(B) side and top views of the prefusion structure of the spike protein of the SARS-CoV-2 with a single RBD in the ascending conformation; the two RBD-down protomers are shown as white or gray cryo-EM density and the RBD-up protomer is shown on ribbons, colored according to the scheme in (A). Image credit: Wrapp et al, doi: 10.1126 / science.abb2507.
Only two weeks after receiving the genome sequence of the SARS-CoV-2 virus, the researchers had designed and produced samples of their stabilized peak protein. It took about 12 more days to reconstruct the 3D atomic scale map, called the molecular structure, of the spike protein.
For the success, state-of-the-art technology known as cryogenic electron microscopy (cryo-EM) was essential, which allows scientists to create atomic-scale 3D models of cell structures, molecules and viruses.
The molecule that produced the equipment, and for which they obtained a structure, represents only the extracellular portion of the spike protein, but is sufficient to elicit an immune response in people and, therefore, serve as a vaccine.
The authors then plan to use their molecule to pursue another line of attack against the SARS-CoV-2 virus, using the molecule as a ‘probe’ to isolate naturally produced antibodies from patients who have been infected with the new coronavirus and recovered with success .
In sufficiently large quantities, these antibodies could help treat a coronavirus infection shortly after exposure. For example, antibodies could protect soldiers or health workers sent to an area with high infection rates in a period too short for the immunity of a vaccine to take effect.