title: 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.
abstract: 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.
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Jieqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Gengfu
authors.initials: G
authors.lastname: Xiao
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Congyi
authors.initials: C
authors.lastname: Zheng
authors.forename: Yueyong
authors.initials: Y
authors.lastname: Liu
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
authors.forename: David K
authors.initials: DK
authors.lastname: Cole
authors.forename: John I
authors.initials: JI
authors.lastname: Bell
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: 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
chemical_list: 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