Structure of the fusion core and inhibition of fusion by a heptad-repeat peptide derived from the S protein of MERS-CoV----中国科学院微生物研究所

科研成果

论文题目:	Structure of the fusion core and inhibition of fusion by a heptad-repeat peptide derived from the S protein of MERS-CoV
作者:	Gao Jing, Lu Guangwen, Qi JianxunLi Yan, Wu Ying, Deng Yao, Geng Heyuan, Li Hongbin, Wang Qihui, Xiao Haixia, Tan Wenjie, Yan Jinghua, George F. Gao*
联系作者:	George F. Gao*
刊物名称:	Journal of Virology
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卷:
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年份:	2013
影响因子:	4.893
论文下载:	http://jvi.asm.org/content/early/2013/09/20/JVI.02433-13.long
摘要:	The Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, the heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized thus far. Here, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical alpha-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 A. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the ground for future inhibitory peptidic drug design.