Discovery of a so-called “cutting-edge” protein that could be a game-changer

In pictures, on an atomic scale, the molecular structure of the “tip” of the SARS-2-CoV protein that the virus uses to invade human cells. Credits: Jason McLellan / University of Texas at Austin

Towards a vaccine or a treatment to fight against the coronavirus

Mutations and changes to create an even more stable molecule

Bibliography:



Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation



Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett, Jory A. Goldsmith, Ching-Lin Hsieh, Olubukola Abiona, Barney S. Graham, Jason S. McLellan



Science 19 Feb 2020:

eabb2507



DOI: 10.1126/science.abb2507

The “tip” protein of the coronavirus has just been mapped, potentially paving the way for the development of a vaccine. In fact, it is this protein that the virus uses to infect human cells.Scientists around the world are currently doing everything they can to develop vaccines and potential drugs to fight the new coronavirus, now known as SARS-CoV-2 (SARS-CoV- 2 in French).But now a group of researchers has discovered the molecular structure of a key protein that the coronavirus uses to invade human cells, potentially opening the door for vaccine development, according to new findings.Previous research has shown that coronaviruses invade cells through so-called “spiked” proteins, but these proteins take different forms in different coronaviruses. Therefore, "determining the shape of the peak protein in SARS-Cov-2 is the key to determining how to target the virus," said Jason McLellan, lead author of the study and associate professor of molecular biosciences at the University of Texas at Austin.Although the coronavirus uses many different proteins to replicate and invade human cells, the spike protein is the main surface protein it uses to bind to a receptor (another protein that acts as a gateway to a human cell). Then, after the virus protein binds to the human cell receptor, the viral membrane fuses with the human cell membrane, allowing the genome of the virus to enter human cells and begin infection.Because of this, "if we can prevent attachment and fusion, we can prevent entry," said McLellan. But of course, to target this protein, you must already know what it looks like.Earlier this month, researchers released the SARS-Cov-2 genome. And it was by using this genome that McLellan and his team, in collaboration with the National Institutes of Health (NIH), identified the specific genes that encode the advanced protein. They then passed this information on to a company that created genes and sent them back. The group then injected the latter into mammalian cells in a laboratory box, and these cells then produced the peak proteins.Then, using a very detailed microscopy technique called cryogenic electron microscopy, the group created a real three-dimensional “map” of the proteins in question.. "It is impressive that these researchers were able to get the structure so quickly," said Aubree Gordon, associate professor of epidemiology at the University of Michigan, who was not part of the study. "This is a very important step forward that could help in the development of a vaccine against SARS-COV-2," added Gordon.Stephen Morse, a professor at Columbia University's Mailman School of Public Health, who was also not part of the study, also agrees. The advanced protein "would be the likely choice for the rapid development of vaccine antigens and treatments," he said. Knowing the structure of this advanced protein would indeed be "very useful for developing vaccines and antibodies with good activity, as well as the production of higher quantities of these proteins".Now the researchers are sending their atomic discovery to dozens of research groups around the world, which are working to develop vaccines and drugs to target SARS-CoV-2. Meanwhile, McLellan and his team also hope to use the advanced protein map as the basis for a vaccine.You should know that when foreign invaders such as bacteria or viruses invade the body, immune cells respond by producing proteins called antibodies. These antibodies bind to specific structures of the foreign invader, called an antigen. But producing antibodies can take time. Vaccines are dead or weakened antigens that cause the immune system to make these antibodies before the body is exposed to the virus.Because of this, in theory, the spike protein itself "could be the vaccine or vaccine variants," said McLellan. Indeed, if we injected this vaccine with advanced proteins, "humans would make antibodies against this advanced protein, and then if they expose themselves one day to the virus, the body would already be prepared", he adds.In addition, building on previous research they have done on other coronaviruses, the researchers have introduced mutations and changes to create a more stable molecule.“The molecule looks really good; she behaves really well; the structure somehow demonstrates that the molecule is stable and confirms what we hoped for," said McLellan. "So now we and others will use the molecule we created as the basis for the vaccine antigen." Their colleagues at NIH will now test these proteins to find out how well they can trigger the production of antibodies.Thanks to this new discovery, researchers believe that a vaccine is likely to be released within 18 to 24 months. "It's pretty quick compared to the normal development of a vaccine, which could take around 10 years ...," said McLellan. A case to follow closely.