Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.
Zheng
Bo-Jion
BJ
Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong SAR, China. bzheng@hkucc.hku.hk
Guan
Yi
Y
Hez
Ming-Liang
ML
Sun
Hongzhe
H
Du
Lanying
L
Zheng
Ying
Y
Wong
Kin-Ling
KL
Chen
Honglin
H
Chen
Ying
Y
Lu
Linyu
L
Tanner
Julian A
JA
Watt
Rory M
RM
Niccolai
Neri
N
Bernini
Andrea
A
Spiga
Ottavia
O
Woo
Patrick C Y
PC
Kung
Hsiang-fu
HF
Yuen
Kwok-Yung
KY
Huang
Jian-Dong
JD
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry*
D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus