Molecular Diversity ( IF 3.9 ) Pub Date : 2021-01-02 , DOI: 10.1007/s11030-020-10171-6 Arpita Devi 1 , Nyshadham S N Chaitanya 2
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Abstract
Short synthetic peptide molecules which bind to a specific target protein with a high affinity to exert its function are known as peptide aptamers. The high specificity of aptamers with small-molecule targets (metal ions, dyes and theophylline; ATP) is within 1 pM and 1 μM range, whereas with the proteins (thrombin, CD4 and antibodies) it is in the nanomolar range (which is equivalent to monoclonal antibodies). The recently identified coronavirus (SARS-CoV-2) genome encodes for various proteins, such as envelope, membrane, nucleocapsid, and spike protein. Among these, the protein necessary for the virus to enter inside the host cell is spike protein. The work focuses on designing peptide aptamer targeting the spike receptor-binding domain of SARS-CoV-2. The peptide aptamer has been designed by using bacterial Thioredoxin A as the scaffold protein and an 18-residue-long peptide. The tertiary structure of the peptide aptamer is modeled and docked to spike receptor-binding domain of SARS CoV2. Molecular dynamic simulation has been done to check the stability of the aptamer and receptor-binding domain complex. It was observed that the aptamer binds to spike receptor-binding domain of SARS-CoV-2 in a similar pattern as that of ACE2. The aptamer–receptor-binding domain complex was found to be stable in a 100 ns molecular dynamic simulation. The aptamer is also predicted to be non-antigenic, non-allergenic, non-hemolytic, non-inflammatory, water-soluble with high affinity toward ACE2 than serum albumin. Thus, peptide aptamer can be a novel approach for the therapeutic treatment for SARS-CoV-2.
Graphical abstract
中文翻译：
靶向SARS-CoV-2刺突蛋白受体结合域的肽适体设计：计算机研究
摘要
以高亲和力结合特定靶蛋白以发挥其功能的短合成肽分子称为肽适体。具有小分子靶标（金属离子、染料和茶碱；ATP）的适体的高特异性在 1 pM 和 1 μM 范围内，而对于蛋白质（凝血酶、CD4 和抗体），它在纳摩尔范围内（相当于单克隆抗体）。最近发现的冠状病毒 (SARS-CoV-2) 基因组编码各种蛋白质，例如包膜、膜、核衣壳和刺突蛋白。其中，病毒进入宿主细胞所必需的蛋白质是刺突蛋白。这项工作的重点是设计针对 SARS-CoV-2 的刺突受体结合域的肽适体。肽适配体是通过使用细菌硫氧还蛋白 A 作为支架蛋白和 18 个残基长的肽而设计的。对肽适体的三级结构进行建模并与 SARS CoV2 的刺突受体结合域对接。已进行分子动力学模拟以检查适体和受体结合域复合物的稳定性。据观察，适体与 SARS-CoV-2 的刺突受体结合域的结合模式与 ACE2 的模式相似。发现适体-受体结合域复合物在 100 ns 分子动力学模拟中是稳定的。该适配体也被预测为非抗原性、非过敏性、非溶血性、非炎症性、水溶性，对 ACE2 的亲和力高于血清白蛋白。因此，肽适体可以成为治疗 SARS-CoV-2 的一种新方法。
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