Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors.
Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is a newly identified member of Family Coronaviridae. Coronavirus envelope spike protein S is a class I viral fusion protein which is characterized by the existence of two heptad repeat regions (HR1 and HR2) (forming a complex called fusion core). Here we report that by using in vitro bio-engineering techniques, SARS-CoV HR1 and HR2 bind to each other and form a typical 6-helix bundle. The HR2, either as a synthetic peptide or as a GST-fusion polypeptide, is a potent inhibitor of virus entry. The results do show that SARS-CoV follows the general fusion mechanism of class I viruses and this lays the ground for identification of virus fusion/entry inhibitors for this devastating emerging virus.
Zhu
Jieqing
J
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
Xiao
Gengfu
G
Xu
Yanhui
Y
Yuan
Fang
F
Zheng
Congyi
C
Liu
Yueyong
Y
Yan
Huimin
H
Cole
David K
DK
Bell
John I
JI
Rao
Zihe
Z
Tien
Po
P
Gao
George F
GF
D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics*; D064370:Spike Glycoprotein, Coronavirus; D013696:Temperature; D014758:Viral Core Proteins / Q000737:chemistry*; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014760:Viral Fusion Proteins / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry
D008562:Membrane Glycoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D064370:Spike Glycoprotein, Coronavirus; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C578557:spike glycoprotein, SARS-CoV; D005982:Glutathione Transferase