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iScience The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike

tetano

Editor, Senior Moderator
iScience


. 2020 May 13;23(6):101160.
doi: 10.1016/j.isci.2020.101160. Online ahead of print.
The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike


Yu Li[SUP] 1 [/SUP], Ziding Zhang[SUP] 1 [/SUP], Li Yang[SUP] 2 [/SUP], Xianyi Lian[SUP] 1 [/SUP], Yan Xie[SUP] 3 [/SUP], Shen Li[SUP] 3 [/SUP], Shuyu Xin[SUP] 2 [/SUP], Pengfei Cao[SUP] 4 [/SUP], Jianhong Lu[SUP] 5 [/SUP]



Affiliations

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 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.

Keywords: Crystallography; Molecular Structure; Virology.
 
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