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

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).Declaration of Interest: The authors declare no conflict of interest.