A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2

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• 作者：Anna-Winona Struck^a ; ¹ ; Marco Axmann^a ; ¹ ; Susanne Pfefferle^b ; ¹ ; Christian Drosten^b ; ^{drosten@virology-bonn.de} ; Bernd Meyer^a ; ^{Bernd.Meyer@chemie.uni-hamburg.de}
• 关键词：SARS coronavirus ; Spike protein ; ACE2 ; Entry inhibitor ; Virus proliferation assay ; SPR screening
• 刊名：Antiviral Research
• 出版年：2012
• 期刊代码：7_01663542
• 类别：imm
• 出版时间：June, 2012
• 卷：94
• 期：3
• 页码：288-296
• 文件大小：585 K

摘要

In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide ⁴³⁸YKYRYL⁴⁴³ is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. ⁴³⁸YKYRYL⁴⁴³ carries the dominant binding epitope and binds to ACE2 with K_D = 46 渭M. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses.