The COVID-19 pandemic revealed the need for therapeutic and pharmaceutical molecule development in a short time with different approaches. Although boosting immunological memory by vaccination was the quickest and robust strategy, still medication is required for the immediate treatment of a patient. A popular approach is the mining of new therapeutic molecules. Peptide-based drug candidates are also becoming a popular avenue. To target whole pathogenic viral agents, peptide libraries can be employed. With this motivation, we have used the 12mer M13 phage display library for selecting SARS-CoV-2 targeting peptides as potential neutralizing molecules to prevent viral infections. Panning was applied with four iterative cycles to select SARS-CoV-2 targeting phage particles displaying 12-amino acid-long peptides. Randomly selected peptide sequences were synthesized by a solid-state peptide synthesis method. Later, selected peptides were analyzed by the quartz crystal microbalance method to characterize their molecular interaction with SARS-CoV-2’s S protein. Finally, the neutralization activity of the selected peptides was probed with an in-house enzyme-linked immunosorbent assay. The results showed that scpep3, scpep8, and scpep10 peptides have both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule. The results of this study have a translational potential with future in vivo and human studies.

中文翻译：

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筛选中和整个病毒制剂的候选肽药物：严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的案例研究

COVID-19 大流行表明需要在短时间内通过不同的方法开发治疗和药物分子。尽管通过疫苗接种来增强免疫记忆是最快和最有效的策略，但仍然需要药物来立即治疗患者。一种流行的方法是挖掘新的治疗分子。基于肽的候选药物也正在成为一种流行的途径。为了靶向整个致病病毒因子，可以使用肽库。出于这个动机，我们使用 12mer M13 噬菌体展示库来选择 SARS-CoV-2 靶向肽作为潜在的中和分子来预防病毒感染。通过四次迭代循环进行淘选，以选择靶向显示 12 个氨基酸长肽的噬菌体颗粒的 SARS-CoV-2。通过固态肽合成方法合成随机选择的肽序列。随后，通过石英晶体微天平方法对选定的肽进行了分析，以表征它们与 SARS-CoV-2 的 S 蛋白的分子相互作用。最后，通过内部酶联免疫吸附测定来探测所选肽的中和活性。结果表明，scpep3、scpep8 和 scpep10 肽对 S1 蛋白具有结合和中和能力，可作为候选治疗分子。这项研究的结果具有未来体内和人体研究的转化潜力。