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

Area of Science:

• Virology
• Molecular Biology
• Bioinformatics

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, highlights gaps in understanding viral pathogenesis.
• Viral entry into host cells is initiated by the attachment of viral proteins to cell-surface receptors and cofactors.
• Identifying these interaction mechanisms is crucial for developing effective countermeasures.

Purpose of the Study:

• To investigate the interaction between SARS-CoV-2 and human cell-surface proteins.
• To elucidate the specific binding mechanisms and residues involved in SARS-CoV-2 attachment.
• To explore potential host factors that influence SARS-CoV-2 infectivity.

Main Methods:

• Utilized bioinformatics approaches for human-virus protein interaction prediction.
• Employed protein docking simulations based on crystal structures.
• Analyzed the spike (S) receptor-binding domain of SARS-CoV-2 for binding affinities.

Main Results:

• Revealed a high affinity interaction between human dipeptidylpeptidase 4 (DPP4) and the SARS-CoV-2 spike protein's receptor-binding domain.
• Identified that crucial DPP4 binding residues are conserved with those interacting with MERS-CoV spike protein.
• Highlighted specific mutations (E484 insertion and adjacent substitutions) in SARS-CoV-2 spike protein as essential for DPP4 binding compared to SARS-CoV.

Conclusions:

• DPP4 is a potential binding target for SARS-CoV-2, offering new insights into viral pathogenesis.
• Understanding this DPP4-SARS-CoV-2 interaction can aid in developing targeted surveillance and therapeutic strategies.
• This finding contributes to the broader effort to combat the COVID-19 pandemic.