The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike
The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike
复制标题
MERS-CoV 受体 DPP4 作为 SARS-CoV-2 刺突的候选结合靶点
DOI：
10.1016/j.isci.2020.101160
复制
发表时间：
2020-06-26
期刊：
影响因子：
5.8
通讯作者：
Lu, Jianhong
中科院分区：
文献类型：
--
作者：
Li, Yu;Zhang, Ziding;Lu, Jianhong
持续爆发的新型冠状病毒肺炎COVID-19已造成大量病例和死亡，但我们对病原体SARS-CoV-2的了解在很大程度上仍不清楚。病毒与细胞表面受体和辅因子的附着是感染的第一步。本文采用生物信息学方法，结合人-病毒蛋白相互作用预测和基于晶体结构的蛋白对接，揭示了人二肽基肽酶4 （DPP4）与SARS-CoV-2刺突(S)受体结合域之间的高亲和力。有趣的是，DPP4的关键结合残基与MERS-CoV-S的结合残基相同。此外，与SARS-CoV-S相比，SARS-CoV-2-S获得dpp4结合能力最重要的是E484的插入和邻近的替换。DPP4作为SARS-CoV-2结合靶点的潜在利用可能为病毒发病机制提供新的见解，并有助于应对COVID-19挑战的监测和治疗策略。
The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a cofactor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidylpeptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those that are bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.