蛋白酶
化学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
肽
绑定域
酶
冠状病毒
结合位点
血浆蛋白结合
2019年冠状病毒病(COVID-19)
生物化学
医学
传染病(医学专业)
疾病
病理
作者
Pengfei Pei,Hongbo Qin,Jialin Chen,Fengli Wang,Chengzhi He,Shiting He,Bixia Hong,Ke Liu,Renzhong Qiao,Huahao Fan,Yigang Tong,Long Chen,Shunzhong Luo
摘要
Abstract Targeting the interaction between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) is believed to be an effective strategy for drug design to inhibit the infection of SARS-CoV-2. Herein, several ultrashort peptidase inhibitors against the RBD–ACE2 interaction were obtained by a computer-aided approach based on the RBD-binding residues on the protease domain (PD) of ACE2. The designed peptides were tested on a model coronavirus GX_P2V, which has 92.2 and 86% amino acid identity to the SARS-CoV-2 spike protein and RBD, respectively. Molecular dynamics simulations and binding free energy analysis predicted a potential binding pocket on the RBD of the spike protein, and this was confirmed by the specifically designed peptides SI5α and SI5α-b. They have only seven residues, showing potent antiviral activity and low cytotoxicity. Enzyme-linked immunosorbent assay result also confirmed their inhibitory ability against the RBD–ACE2 interaction. The ultrashort peptides are promising precursor molecules for the drug development of Corona Virus Disease 2019, and the novel binding pocket on the RBD may be helpful for the design of RBD inhibitors or antibodies against SARS-CoV-2.
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