Identification of a minimal peptide derived from heptad repeat (HR) 2 of spike protein of SARS-CoV and combination of HR1-derived peptides as fusion inhibitors.
The heptad repeats (HR1 and HR2) of the spike protein of SARS-CoV are highly conserved regions forming a critical 6-helix bundle during the fusion step of virus entry and are attractive targets of entry inhibitors. In this study, we report that a minimal HR2 peptide, P6 of 23-mer, can block the fusion of SARS-CoV with an IC(50) of 1.04+/-0.22 microM. This finding supports the structural prediction of the deep groove of HR1 trimer as a target for fusion inhibitors, and suggests P6 as a potential lead peptide for future drug development. Moreover, combination of an HR-1 peptide, N46, and its mutated version, N46eg, shows synergistic inhibition with an IC(50) of 1.39+/-0.05 microM and combination index of 0.75+/-0.15, suggesting a common strategy to achieve promising inhibition by HR1 peptide for other class I envelope viruses.
Liu
I-Jung
IJ
Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Kao
Chuan-Liang
CL
Hsieh
Szu-Chia
SC
Wey
Ming-Tsair
MT
Kan
Lon-Sing
LS
Wang
Wei-Kung
WK
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects*
D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins