Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus

文献作者：Yaping Sun, Huaidong Zhang , Jian Shi , Zhe Zhang, Rui Gong  《VIRUSES》

ABSTRACTS

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.

KEY WORDS

MERS-CoV; fusion inhibitor; six-helix bundle; heptad repeat; five-helix bundle

SCREENSHOT

RELATED PRODUCTS

In order to determine the interaction between MERS-5HB and HR2, we synthesized a biotin-labeled peptide MERS-HR2P representative of HR2 by the standard solid phase peptide synthesis method with purity above 95% (ChinaPeptides, Shanghai, China).

CHAINING

http://www.mdpi.com/1999-4915/9/9/255/htm