Li Yu, Zhang Ziding, Yang Li, Lian Xianyi, Xie Yan, Li Shen, Xin Shuyu, Cao Pengfei, Lu Jianhong
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Department of Hematology, Xiangya Hospital, Central South University, Changsha 410080, China; Department of Microbiology, School of Basic Medical Science, Central South University, Changsha 410078, China; China-Africa Research Center of Infectious Diseases, Central South University, Changsha 410013, China.
iScience. 2020 Jun 26;23(6):101160. doi: 10.1016/j.isci.2020.101160. Epub 2020 May 13.
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.
新型冠状病毒肺炎（COVID-19）的持续爆发已导致大量病例和死亡，但我们对病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的了解仍大多不清楚。病毒与细胞表面受体及一种辅助因子的结合是感染的第一步。在此，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的生物信息学方法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的关键结合残基与那些与中东呼吸综合征冠状病毒S（MERS-CoV-S）结合的残基相同。此外，与严重急性呼吸综合征冠状病毒S（SARS-CoV-S）相比，E484插入及相邻替换对于SARS-CoV-2-S获得这种DPP4结合能力应该最为关键。DPP4作为SARS-CoV-2结合靶点的这种潜在用途可能为病毒发病机制提供新见解，并有助于应对COVID-19挑战的监测和治疗策略。
