Division of Infectious Diseases and Division of Computer-Aided Drug Design, The Red-Green Research Centre, BICCB, 16 Tejkunipara, Tejgaon, Dhaka 1215, Bangladesh.
Department of Pharmacy, Southeast University, Dhaka 1213, Bangladesh.
J Phys Chem B. 2020 Nov 5;124(44):9785-9792. doi: 10.1021/acs.jpcb.0c05621. Epub 2020 Oct 23.
Over 50 peptides, which were known to inhibit SARS-CoV-1, were computationally screened against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Based on the binding affinity and interaction, 15 peptides were selected, which showed higher affinity compared to the α-helix of the human ACE2 receptor. Molecular dynamics simulation demonstrated that two peptides, S2P25 and S2P26, were the most promising candidates, which could potentially block the entry of SARS-CoV-2. Tyr489 and Tyr505 residues present in the "finger-like" projections of the RBD were found to be critical for peptide interaction. Hydrogen bonding and hydrophobic interactions played important roles in prompting peptide-protein binding and interaction. Structure-activity relationship indicated that peptides containing aromatic (Tyr and Phe), nonpolar (Pro, Gly, Leu, and Ala), and polar (Asn, Gln, and Cys) residues were the most significant contributors. These findings can facilitate the rational design of selective peptide inhibitors targeting the spike protein of SARS-CoV-2.
针对 SARS-CoV-2 刺突蛋白的受体结合域（RBD），计算机筛选了超过 50 种已知能抑制 SARS-CoV-1 的肽。根据结合亲和力和相互作用，选择了 15 种肽，其与人类 ACE2 受体的α螺旋相比显示出更高的亲和力。分子动力学模拟表明，两种肽，S2P25 和 S2P26，是最有前途的候选物，它们有可能阻止 SARS-CoV-2 的进入。在 RBD 的“指状”突起中存在的 Tyr489 和 Tyr505 残基被发现对肽相互作用至关重要。氢键和疏水相互作用在促使肽-蛋白结合和相互作用中发挥了重要作用。构效关系表明，含有芳香族（Tyr 和 Phe）、非极性（Pro、Gly、Leu 和 Ala）和极性（Asn、Gln 和 Cys）残基的肽是最重要的贡献者。这些发现可以促进针对 SARS-CoV-2 刺突蛋白的选择性肽抑制剂的合理设计。
