Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction.
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.
Ho
Tin-Yun
TY
Molecular Biology Laboratory, Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.
Wu
Shih-Lu
SL
Chen
Jaw-Chyun
JC
Wei
Yen-Chiao
YC
Cheng
Shin-Ei
SE
Chang
Yung-Hsien
YH
Liu
Hsu-Jan
HJ
Hsiang
Chien-Yun
CY
D000595:Amino Acid Sequence; D000818:Animals; D019921:Biotinylation; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism* / Q000472:pathogenicity; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C066778:ACE2 protein, S cerevisiae; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D064370:Spike Glycoprotein, Coronavirus; D014157:Transcription Factors; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus