Nature Com. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor

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Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor

Lu Lu1, 5
Qi Liu1, 5
Yun Zhu2, 5
Kwok-**** Chan3
Lili Qin2
Yuan Li1
Qian Wang1
Jasper Fuk-Woo Chan3
Lanying Du4
Fei Yu4
Cuiqing Ma4
Sheng Ye2
Kwok-Yung Yuen3
Rongguang Zhang2
Shibo Jiang1, 4



Nature Communications
5,
Article number:
3067
doi:10.1038/ncomms4067


Abstract



A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998–1039 in HR1 and 1251–1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell–cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection.

http://www.nature.com/ncomms/2014/140128/ncomms4067/full/ncomms4067.html

 

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Re: Nature Com. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor

Source: http://www.newscientist.com/article...RSS|NSNS|2012-GLOBAL|online-news#.UugVBPZOmhc

Deadly MERS virus could hold the key to its own cure
16:58 28 January 2014 by Debora MacKenzie

A piece of the deadly MERS virus might provide its own cure.

The virus causing Middle East respiratory syndrome emerged in 2012. It does not spread readily between people, but there are fears it could cause a pandemic if it ever starts. It has killed 76 of the 178 people known to have caught it so far, and there is no specific treatment.

Shibo Jiang at Fudan University in Shanghai and his colleagues found that the virus forces its way into cells using a rod-like structure made of two "fusion" proteins on the virus surface that bind tightly to each other during infection...