埃博拉病毒 z-bo 2020-09-21 381

　　Ebola virus is a biosafety level 4 (biosafety level 4) virus that can cause diseases in humans and primates, and has a high fatality rate. According to statistics from the World Health Organization, the Ebola virus has spread in Africa for nearly 40 years since it was first discovered in 1976. Since March 2014, the Zaire-type Ebola virus epidemic, particularly in Guinea, Liberia and Sierra Leone, has spread rapidly throughout West Africa, causing more than 28,000 infections and nearly 11,000 deaths.

　　In 2014, Ebola hemorrhagic fever occurred in West Africa. The Chinese government sent the first batch of 62 workers to form the first mobile laboratory testing team and went to Sierra Leone. Aka Demian Gao Fu (Aka Demian Gao Fu) was appointed as the former deputy team leader of the laboratory testing team of the Chinese Center for Disease Control and Prevention. He is mainly responsible for the communication and promotion of "Science" magazine with international institutions. Published documentary articles about the work of "Walking on the Land of Sierra Leone" and "On the Grading Sierra Leone".

　　"We have published important discoveries about the genetic evolution of (natural) Ebola virus. Ebola virus is an enveloped virus. Ebola virus can divide the host invasion into two important steps. First, the virus attaches to The surface of the host cell membrane, then enters the cell through endocytosis and forms an endosome; in endocytosis, the virus releases its genetic material through the process of membrane fusion. Human TIM molecules are a class of immune molecules that are widely distributed in immune cells. It plays an important role in regulating the immune response (such as allergy, asthma, transplant resistance and autoimmunity). Previously, a study by the Gaofu Research Institute found that human TIM molecules are not directly related to the glycoprotein on the surface of the Ebola virus envelope. It interacts, but promotes virus infection by binding to the phosphatidylserine molecule on the virus envelope. The results were published in the 35th issue of China’s top journal "Science Bulletin" in 2015 with the title "Ebola virus invasion: human The molecular basis of the structure of the TIM molecule and the combination of PS". It was published as a cover article. On this basis, the Gaofu College team further studied the mechanism of Ebola virus invading the endosome after entering the cell. Previous studies found that the internal An NPC molecule on the swallowing membrane is necessary for the invasion of Ebola virus. However, how an NPC molecule mediates the invasion of the virus has always been an unsolved mystery. The PC1 molecule is a multi-membrane protein involved in cholesterol transport. Three large intraluminal domains (A, C and I). The glycoprotein on the surface of the Ebola virus envelope is digested by the endosomal host protease cathepsin and becomes an activated glycoprotein, which exposes the receptor binding site It also interacts with the intraluminal domain C of the NPC1 molecule, and then interacts with the viral membrane. The fusion process begins to realize the life history of viral infection.

　　The research team led the analysis of the three-dimensional structure of the intracavity domain C of an NPC molecule and found that it has a spherical core domain composed of α helix and β sheet and two prominent loop structures. The researchers then analyzed the three-dimensional structure of the complex between activated glycoprotein and intraluminal domain C, where domain C uses two main protruding loop structures to form the head of the activated glycoprotein. I found it inserted into the drain groove. Interaction occurs. This main finding indicates that people can design small molecules or peptide inhibitors to activate the hydrophobic groove on the head of glycoproteins to prevent the invasion of Ebola virus. Further analysis showed that after the activated glycoprotein binds to intraluminal domain C, structural changes occur, which increases the possibility that glycoprotein fusion peptides are exposed and inserted into the endosomal membrane to initiate the membrane fusion process.