What happened at the moment when the new coronavirus infected the human body? West Lake University has made a great breakthrough again!

Zhou Qiang Laboratory of West Lake University has made a great breakthrough again In the early morning of February 21, Beijing time, Zhou Qiang's research team published another paper on biorxiv, the website of paper preprint, reporting the complex structure of S protein receptor binding domain on the surface of new coronavirus and ACE2 full-length protein on the cell surface, revealing the mystery of new coronavirus invading human cells Just two days ago, the team just published the full-length structure of the new coronavirus receptor ACE2 on biorxiv The first author of these two preprinted papers is Yan Renhong, a postdoctoral fellow of the school of life sciences of West Lake University, and the corresponding author is Zhou Qiang, a researcher of the school of life sciences of West Lake University The first unit and communication unit are the Key Laboratory of structural biology of Zhejiang Province, West Lake University The novel coronavirus pneumonia prevention and treatment project undertaken by West Lake university is also an important achievement of Zhejiang Province, which has been strongly supported by Zhejiang, Hangzhou relevant departments and Xihu District This novel coronavirus caused by ACE2 and S protein has been the new form of pneumonia, and the common biological terms such as coronavirus, S protein and ACE2 have once again entered the public view It is found that novel coronavirus is the key to infecting human cells, which is the combination of S protein and human ACE2 protein To be precise, it is s protein that hijacks ACE2, which is originally used to control blood pressure, and invades human body through its combination S protein is called spike glycoprotein, which is located in the outermost layer of the new coronavirus, like a "crown" According to the latest analytical results of the research team at the University of Texas Austin, the new coronavirus s protein exists in the form of trimer There are about 1300 amino acids in each monomer, and more than 300 amino acids constitute the "receptor binding domain" (RBD), which is the place where S protein and ACE2 are linked Ace2-b0at1 complex is a protein involved in the regulation of blood pressure in human body It is widely found in the lung, heart, kidney and intestine How can the protein of a human cell contact with a virus? Tao Liang, a special researcher of West Lake University, used an image metaphor: "if you think of the human body as a house and the new coronavirus as a robber, then ACE2 is the" door handle "of this house; s protein catches it and the virus goes straight into the human cells." How does s protein grasp ACE2? Although s protein and ACE2 are the front line of contact between the enemy and us, before the outbreak, scientists had never seen the whole picture of ACE2 and the interaction between ACE2 and S protein of new coronavirus Two days ago, Zhou Qiang took the lead in reporting the high-resolution three-dimensional spatial structure of ACE2 full-length protein in the world This time, they further resolved the complex structure of ACE2 full-length protein and S-protein receptor binding domain of new coronavirus The receptor resolution was 2.9 angstroms, and the resolution of S-protein receptor binding domain was 3.5 angstroms Rbd-ace2-b0at1 composite structure diagram, then, what do they see in the analyzed composite structure? They found that in morphology, the S protein of the new coronavirus is like a bridge across the surface of ACE2, like a hand of the virus, tightly holding on to ACE2, which is similar to the SARS virus The receptor binding domain of S protein of new coronavirus is very similar to that of SARS virus, and the similarity is 82% Further analysis of the interaction between the receptor binding domain (RBD) of S protein of new coronavirus and ACE2 showed that the researchers could see which amino acids interact with ACE2 on the surface of new coronavirus Compared with the interaction between SARS virus and ACE2, a part of amino acid residues of S protein of new coronavirus changed greatly This may explain why the binding ability of SARS and ACE2 is different, which may affect the infectivity of the virus However, whether it is enhanced or weakened needs to be verified by other experimental means The structure of novel coronavirus S protein is compared with that of RBD-ACE2-B0AT1 complex, and the two are anchored by RBD domain (left, new coronavirus 2019-nCoV, right, SARS-CoV) It is reported that the research team of Professor Wang Xinquan of Tsinghua University and Qi Jianxun of Institute of Microbiology of Chinese Academy of Sciences independently analyzed the crystal structure of the N-terminal protease domain of ACE2 and the S-protein receptor binding domain of new coronavirus These information and the electron microscope structure of Zhou Qiang's team support and complement each other It is worth mentioning that all three independent teams choose to publish the atomic coordinates of their compounds to the whole society in the first time, so as to improve their possible utilization The atomic coordinates of the complexes of the ACE2 full-length protein and the new coronavirus S-protein receptor binding domain of the Zhou Qiang team of West Lake University can be downloaded from the following website: https://www.jianguoyun.com/p/dvlsdkqij2ocbjbwt8c the atomic coordinates of the complexes of the ACE2 protease domain and the new coronavirus S-protein receptor binding domain of the Wang Xinquan team of Tsinghua University can be downloaded from the following website: The atomic coordinates of the complex of ACE2 protease domain and S-protein receptor binding domain of new coronavirus can be downloaded from the following website: http://nmdc.cn/resource/detail? No = nmdcs00000001 The atomic coordinates of ACE2 full-length protein and amino acid transporter of Zhou Qiang's team of West Lake University can be downloaded from the following website, in closed state: https://www.jianguoyun.com/p/dsjqlq4qij2ocbjcwt8c in open state: https://www.jianguoyun.com/p/dwdo-qmqij2ocbjgwt8c how far are we from the "special drug" The density map of rbd-ace2-b0at1 complex under freeze electron microscope shows that the interaction interface between RBD and ACE2 started at the end of 2019, and the pneumonia caused by the new coronavirus has gradually slowed down However, due to the lack of specific drugs for viruses, the public is looking forward to the scientific research related to viruses Zhou Qiang's team said that the analysis of the structure of the complex is a breakthrough in the field of basic research, and has no inevitable connection with the research and development of anti epidemic drugs But on the other hand, it's really important Because the structure of the protein determines its nature and function to a large extent, to see the structure of S protein, ACE2 and their interaction of the new coronavirus is equivalent to seeing the "enemy's appearance", which provides more information for the follow-up scientists' targeted drug research Only knowing one's own and knowing the other can one hundred battles be invincible Another significance of this research is that researchers of computational biology can build different models based on this, and then carry out targeted research to determine what kind of mutation may further improve the interaction between S protein and ACE2, so as to design drugs and antibodies against S protein or ACE2 protein; or design small molecules to destroy the Interaction All of these provide a solid foundation for drug design and development of detection methods The research in the field of basic science is a long process, which needs to be adhered to in obscurity In fact, in the past two years, Zhou Qiang laboratory has been studying human amino acid transporters They have targeted several kinds of target proteins, among which ACE2 is one After the outbreak of novel coronavirus pneumonia, Zhou Qiang team quickly raised the priority of ACE2 research, and achieved the research results with the fastest speed, providing the key information for later drug development Reference source: structural basis for the recognition of the 2019-ncov by human ace2rennong Yan, Yuanyuan Zhang, Yingying Guo, Lu Xia, Qiang Zhou https://www.biorxiv.org/content/10.1101/2020.02.19.956946v1 Jenny turtle