Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein.
Heptad repeat regions (HR1 and HR2) are highly conserved sequences located in the glycoproteins of enveloped viruses. They form a six-helix bundle structure and are important in the process of virus fusion. Peptides derived from the HR regions of some viruses have been shown to inhibit the entry of these viruses. SARS-CoV was also predicted to have HR1 and HR2 regions in the S2 protein. Based on this prediction, we designed 25 peptides and screened them using a HIV-luc/SARS pseudotyped virus assay. Two peptides, HR1-1 and HR2-18, were identified as potential inhibitors, with EC(50) values of 0.14 and 1.19microM, respectively. The inhibitory effects of these peptides were validated by the wild-type SARS-CoV assay. HR1-1 and HR2-18 can serve as functional probes for dissecting the fusion mechanism of SARS-CoV and also provide the potential of further identifying potent inhibitors for SARS-CoV entry.
Yuan
Kehu
K
Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, PR China.
Yi
Ling
L
Chen
Jian
J
Qu
Xiuxia
X
Qing
Tingting
T
Rao
Xi
X
Jiang
Pengfei
P
Hu
Jianhe
J
Xiong
Zikai
Z
Nie
Yuchun
Y
Shi
Xuanling
X
Wang
Wei
W
Ling
Chen
C
Yin
Xiaolei
X
Fan
Keqiang
K
Lai
Luhua
L
Ding
Mingxiao
M
Deng
Hongkui
H
D000595:Amino Acid Sequence; D001681:Biological Assay; D002460:Cell Line; D002942:Circular Dichroism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D008562:Membrane Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins