The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike
iScience
23 Pages Posted: 13 Apr 2020 Sneak Peek Status: Under Review
Yu Li
China Agricultural University - State Key Laboratory of Agrobiotechnology
Ziding Zhang
China Agricultural University - State Key Laboratory of Agrobiotechnology
Li Yang
Central South University - Department of Hematology
Xianyi Lian
China Agricultural University - State Key Laboratory of Agrobiotechnology
Yan Xie
Central South University - Department of Hematology
Shen Li
Central South University - Department of Hematology
Shuyu Xin
Central South University - Department of Hematology
Pengfei Cao
Central South University - Department of Hematology
Jianhong Lu
Central South University - Department of Hematology
Abstract
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 co-factor is the firstly important 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 dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 at the interface are identical to those as bound to the MERS-CoV spike. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with that of SARS-CoV-S, which does not interact with DPP4. This potential utilization of DPP4 as a coreceptor or 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.
Funding: This work was supported by the National Key Research and Development Program and the National Natural Science Foundations of China (2017YFC1200204, 2017YFC1200205, 31670171 and 81974427).
