Ebola virus is one of the deadliest viruses in the world. Ebola virus polymerase is responsible for the viral genome replication process and is highly conservative. It is an important target for the development of broad-spectrum drugs. However, due to the large molecular weight, instability, and easy degradation, the analysis of the three-dimensional structure of Ebola virus polymerase has always been a global problem, which seriously restricts the development of drugs targeting polymerases.
High Fu /Shi Yi team of the Institute of Microbiology, Chinese Academy of Sciences Gaofu /Shi Yi team first analyzed the structure of Ebola virus polymerase, clarified the molecular mechanism of its synthetic progeny RNA, and clarified the dynamic changes in the transition from the starting state to the extension state when transcribed and replicated by segmented negative strand RNA virus , laying a key theoretical foundation for understanding the Ebola virus replication mechanism from the molecular level; at the same time, this work found that sulamin drugs can effectively inhibit the activity of Ebola virus polymerase by inhibiting NTP substrates from entering the enzyme activity center, which not only provides a candidate treatment plan for the prevention and control of the Ebola epidemic, but also provides new targets and directions for the development of anti-Ebola virus drugs.
This research result was published in Nature magazine on September 28, 2022. Hong Kong Institute of Microbiology, Chinese Academy of Sciences Doctoral student Yuan Bin and researcher Peng Qi are the co-first authors of this article, and postdoctoral fellow Cheng Jinlong and researcher Wang Min also participated in the study. Researchers from the Institute of Microbiology, Chinese Academy of Sciences, Academician Shi Yi and Gao Fu are the corresponding authors of in this article. This work also received strong support from researcher Qi Jianxun, Institute of Microbiology, Chinese Academy of Sciences, and Zhong Jin, researcher at the Shanghai Pasteur Institute. The research has been supported by projects such as the National Key R&D Plan, the Strategic Pioneer Project of the Chinese Academy of Sciences, the National Natural Science Foundation of and the Chinese Academy of Sciences Youth Innovation Promotion Association and other projects.
Paper link: https://www.nature.com/articles/s41586-022-05271-2
