Abstract
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). The binding of SARS-CoV spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2) is the first step in SARS-CoV infection. Therefore, we assayed the inhibitory effects of small peptides derived from S protein on the binding of S protein to ACE2 and on the S-protein-pseudotyped retrovirus infectivity. SP-4 (residues 192-203), SP-8 (residues 483-494), and SP-10 (residues 668-679) significantly blocked the interaction between S protein and ACE2 by biotinylated enzyme-linked immunosorbent assay, with IC(50) values of 4.30 +/- 2.18, 6.99 +/- 0.71, and 1.88 +/- 0.52 nmol, respectively. Peptide scanning suggested the region spanning residues 660-683 might act as a receptor-binding domain. SP-10 blocked both binding of the S protein and infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. In conclusion, this is the first report of small peptides designed to disrupt the binding of SARS-CoV S protein to ACE2. Our findings suggest that SP-10 may be developed as an anti-SARS-CoV agent for the treatment of SARS-CoV infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Biotinylation
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Chlorocebus aethiops
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Humans
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Molecular Sequence Data
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors
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Saccharomyces cerevisiae Proteins / metabolism*
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Severe Acute Respiratory Syndrome / virology
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Severe acute respiratory syndrome-related coronavirus / metabolism*
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Severe acute respiratory syndrome-related coronavirus / pathogenicity
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Spike Glycoprotein, Coronavirus
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / metabolism*
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Vero Cells
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Viral Envelope Proteins / antagonists & inhibitors*
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Viral Envelope Proteins / chemistry
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism*
Substances
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ACE2 protein, S cerevisiae
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DNA-Binding Proteins
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Membrane Glycoproteins
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Peptides
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Spike Glycoprotein, Coronavirus
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Transcription Factors
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Viral Envelope Proteins
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spike glycoprotein, SARS-CoV
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spike protein, mouse hepatitis virus