埃博拉病毒病 z-bo 2020-12-16 379

　　Ebola virus disease is an acute hemorrhagic infectious disease caused by Ebola virus (EBOV) of the filoviridae family. The fatality rate of this disease is extremely high, reaching 50%-90%. It is one of the deadliest viral infectious diseases of mankind. Statistics from the World Health Organization show that from the end of 2013 to 2015, more than 22,500 people were infected with the Ebola virus in the Ebola outbreak in West Africa, and the number of people who died as a result of the infection reached 9,000. Regardless of the number of infected cases, the number of deaths, or the scope of the affected area, they have reached the largest scale since the virus was discovered in 1976. On August 8, 2014, the EBOV outbreak was officially regarded as a public health emergency of high international concern. Currently, no country in the world has effective drugs and treatments to control the Ebola epidemic. NSR recently published a joint article "New targets for controlling Ebola virus disease" by Professor Qin Xiaofeng, Professor Jiang Taijiao, Professor Cheng Genhong, and Professor Jiang Chengyu from the Institute of Basic Medicine, Chinese Academy of Medical Sciences, Suzhou Institute of System Medicine, Chinese Academy of Medical Sciences. ://nsr.oxfordjournals.org/content/2/3/266.full). This article combines the life cycle of Ebola virus and analyzes the potential inhibition of Ebola virus by 25-hydroxyl cholesterol (25-hydroxyl cholesterol, 25HC) and other natural immune antiviral small molecules The role, from the perspective of preventing Ebola virus infection, expounds the progress of the research strategy of new drug targets, and uses the methods of systems biology to illustrate the pathogen-host interaction.

　　The article first introduced the research progress of small molecule inhibitors that target the process of Ebola virus invading host cells. Unlike other enveloped viruses, Ebola virus invades the inside of cells by inducing cells to initiate macropinocytosis (Macropinocytosis). Recent studies have shown that the two-pore channel (TPC) protein family plays an important role in the process of Ebola virus invading host cells, and the small molecule compound Tetrandrine can potentially specifically inhibit the TPC channel, thereby hindering the virus invasion process. Therefore, similar to TPCs, other small molecule inhibitory drugs that target virus invasion need to be further studied. At the same time, the host-encoded interferon induces the ISG protein to have a strong natural immune function against viral infection. The author's laboratory research results show that cholesterol-25 hydroxylase (Cholesterol-25-hydroxylase, CH25H) can convert cholesterol into a soluble factor, 25 hydroxy cholesterol (25HC). In the P-4 biosafety level study, it was proved that 25HC can significantly reduce the infection of wild-type EBOV (Zaire Strain, Zaire strain) on human cells, showing that it has great potential as a new type of emergency treatment for Ebola virus infection .

　　 In addition to targeting the virus invasion process, the article also describes the research progress of drugs that target the process of virus budding from host cells and releasing soluble proteins from infected cells. Among them, the Ebola virus GP protein, whether it is covered on the surface of the virus or shed from infected cells during the infection process, can participate in a variety of immune responses and play an important role in the virus life cycle and host-pathogen interaction. The role is a potential and effective target to inhibit the process of Ebola virus infection, replication and pathogenesis.

　　 At present, it is urgent to develop and prepare efficient, safe and fast-acting drugs to treat Ebola virus for the country's emergency strategic reserve of small molecule drugs to fight against the infection and spread of EBOV virus. Small molecule inhibitory drugs targeting different targets to further elucidate the pathogenesis of Ebola virus disease need further research.