De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein,ACS Central Science

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De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
ACS Central Science ( IF 12.7 ) Pub Date : 2020-12-17 , DOI: 10.1021/acscentsci.0c01309
Sebastian Pomplun ₁ , Muhammad Jbara ₁ , Anthony J Quartararo ₁ , Genwei Zhang ₁ , Joseph S Brown ₁ , Yen-Chun Lee ₁ , Xiyun Ye ₁ , Stephanie Hanna ₁ , Bradley L Pentelute _{1,

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Affiliation

The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein are of interest for the development of therapeutics and diagnostics. We used affinity selection–mass spectrometry for the rapid discovery of synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants K_d = 80–970 nM) for RBD and selectivity over human serum proteins. Nanomolar RBD concentrations in a biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides do not compete for ACE2 binding, and their site of interaction on the SARS-CoV-2-spike-RBD might be unrelated to the ACE2 binding site, making them potential orthogonal reagents for sandwich immunoassays. These findings serve as a starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus-directed delivery of therapeutics.

中文翻译：

从头发现 SARS-CoV-2 刺突蛋白的高亲和力肽结合剂

β-冠状病毒 SARS-CoV-2 已引起全球大流行。针对 SARS-CoV-2 刺突蛋白的亲和试剂对于治疗和诊断的开发很有意义。我们使用亲和力选择-质谱法快速发现 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 的合成高亲和力肽结合剂。通过对 8 亿条合成肽进行文库筛选，我们鉴定了 3 条 RBD 亲和力（解离常数K _d = 80-970 nM）的序列，以及对人血清蛋白的选择性。可以使用 ELISA 格式的生物素化先导肽来检测生物基质中的纳摩尔 RBD 浓度。这些肽不会竞争 ACE2 结合，并且它们在 SARS-CoV-2-spike-RBD 上的相互作用位点可能与 ACE2 结合位点无关，这使它们成为夹心免疫测定的潜在正交试剂。这些发现可以作为开发 SARS-CoV-2 诊断方法或用于病毒定向治疗递送的结合物的起点。

更新日期：2021-01-27

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