SARS-CoV-2刺突蛋 z-bo 2020-10-30 448

　　In a new study, researchers from the Francis-Crick Institute in the United Kingdom found that the spike protein (S protein) on the surface of the SARS-CoV-2 coronavirus can be used when it comes into contact with the human virus receptor ACE2. At least ten different structural states. This new insight into the mechanism of infection lays the foundation for the development of vaccines and treatments. The relevant research results were published online on September 17, 2020 in the journal Nature, with the title of the paper "Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion".

　　As the coronavirus that causes new coronary pneumonia (COVID-19), the surface of SARS-CoV-2 is covered with S protein, which allows this virus to infect human cells. When the S protein binds to the cell surface receptor ACE2 and catalyzes the release of the viral genome into the cell at a later stage, the infection begins. However, the exact nature of the binding of ACE2 to the S protein of SARS-CoV-2 is still unknown.

　　In the first overall study of the binding mechanism between ACE2 and S protein, these researchers characterized 10 different structures related to S protein binding to receptors and different stages of infection. They first incubate a mixture of S protein and ACE2, and then quickly freeze them in liquid ethane to capture different forms of S protein. They used cryo-electron microscopy to examine these protein samples and obtained tens of thousands of high-resolution images of different binding stages.

　　They observed that S protein exists as a mixture of closed and open structures. After ACE2 binds to an open site, the S protein becomes more open, leading to a series of favorable conformational changes to prepare for further binding. Once the S protein binds to ACE2 at all three binding sites, its central core will be exposed, which may help SARS-CoV-2 to fuse with the cell membrane, allowing infection to occur.

　　Donald Benton, co-corresponding author of the paper and a postdoctoral training researcher at the Structural Biology Laboratory of the Francis-Crick Institute of Disease Processes, said, “By studying the binding events from a holistic perspective, we can describe the structure of SARS-CoV-2's unique S protein. We It can be observed that when the S protein becomes more open, the stability of this protein will decrease, which may increase its ability to perform membrane fusion, thereby allowing infection to occur."

　　These researchers hope that the more they can discover the difference between SARS-CoV-2 and other coronaviruses, the more targeted they can develop new treatment methods and vaccines.

　　Antoni Wrobel, co-corresponding author of the paper and a postdoctoral training researcher in the Structural Biology Laboratory of the Francis-Crick Institute of Disease Processes, said, “As we uncover the mechanisms of the earliest stages of infection, we may expose new therapeutic targets, or Understand which antiviral therapies currently available are more likely to work."

　　Steve Gamblin, co-corresponding author of the paper and head of the Structural Biology Laboratory of the Francis-Crick Institute of Disease Processes, said, “We still have a lot of knowledge about SARS-CoV-2, but its basic biology includes control. Clues to this epidemic. By understanding what makes this virus unique, we can expose exploitable weaknesses." These researchers are continuing to study SARS-CoV-2 and related coronaviruses in other species. Protein structure to better understand the mechanism of virus infection and evolution.