Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus
AbstractThe 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. View Full-Text
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Sun, Y.; Zhang, H.; Shi, J.; Zhang, Z.; Gong, R. Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus. Viruses 2017, 9, 255.
Sun Y, Zhang H, Shi J, Zhang Z, Gong R. Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus. Viruses. 2017; 9(9):255.Chicago/Turabian Style
Sun, Yaping; Zhang, Huaidong; Shi, Jian; Zhang, Zhe; Gong, Rui. 2017. "Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus." Viruses 9, no. 9: 255.
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