Author: Ye Bu Release Date: 2019-01-18
Yellow fever is a natural epidemic disease transmitted by mosquito vectors. It has the characteristics of rapid onset, strong contagiousness and high mortality. It has been designated as an international quarantine infectious disease by the World Health Organization. So far, there is no specific treatment for yellow fever in the international arena. Recently, the Protein Engineering and Vaccine Research Team of the Tianjin Institute of Industrial Biology, led by the Chinese Academy of Sciences, Gao Fu, has made significant progress in the study of the structure and therapeutic antibodies of the yellow fever virus E protein. The relevant research results are "one strain against the yellow fever virus capsule. The protein's "double-locked" human-neutral neutralizing and protective monoclonal antibodies are published online in Cell-Reporting.
Tianjin Haixia, a deputy researcher at the Tianjin Institute of Industrial Biology, told the Journal of the Chinese Academy of Sciences that the YFV17D live attenuated vaccine can effectively prevent the infection of yellow fever virus. However, factors such as vaccine shortages and limited immunization coverage have led to the emergence and prevalence of yellow fever. In addition, infectious diseases caused by the Flavivae family, such as dengue fever, which have similar symptoms to yellow fever, also increase the difficulty of drug development.
In recent years, monoclonal antibodies have shown great advantages and potential applications as drug candidates for the treatment of viral infectious diseases. It has been found that the envelope protein of the yellow fever virus (E protein) mediates viral invasion into host cells and is a major protective antigen and neutralizing antibody target. The field of research conjectures that neutralizing antibodies against yellow fever virus can inhibit viral invasion by inhibiting adhesion of the virus to host cells or fusion of viral envelope membranes with cell membranes.
In order to explore the mechanism of action of neutralizing antibodies, to verify whether the antibody has effect on the virus, Gao Fu and his research team first analyzed the high-resolution yellow fever virus vaccine strain YF-17D before the membrane E protein fusion and fusion The latter two forms of crystal structure. The study found that the pre-fusion E protein of the yellow fever virus showed a dimeric conformation, which was similar to the structure of the E protein of other members of the Flavivirus genus. Under low pH conditions, the E protein of the yellow fever virus is in the conformation of the trimeric conformation, and the conformation of the E protein after fusion with the dengue virus and the tick-borne encephalitis virus is similar.
In addition, the researchers conducted an in-depth study of the function, structure, and neutralization mechanism of the yellow fever virus-specific neutralizing antibody 5A. The study found that 5A has a very high potency to neutralize the yellow fever virus and protects the mice against lethal doses of the yellow fever virus. Structural analysis also found that 5A can combine both the E protein dimer before fusion and the E protein trimer after fusion, like a "double lock". Further functional experiments have also confirmed that 5A can act at multiple stages of viral invasion: blocking the adsorption of the virus on host cells, inhibiting the E protein allosteric and fusion peptide insertion necessary for membrane fusion. This result confirms the "double-lock" mechanism of action of the 5A super-neutralizing virus. According to Xue Haixia, the research will provide a theoretical basis for the design of small molecule drugs such as yellow fever virus peptides and immunogens.
Source: Science Network
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