The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike

SUMMARY

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 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 dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as 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.

Graphical Abstract

Highlights

• SARS-CoV-2 spike receptor-binding domain has a potentially high affinity with DPP4

• SARS-CoV-2-S/DPP4 binding shares key DPP4 residues with that of MERS-CoV-S/DPP4

• E484 and adjacent mutations are critical for the DPP4-binding ability of SARS-CoV-2-S