A comprehensive PDCoV-host proteome interaction map reveals potential antiviral targets

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Porcine deltacoronavirus (PDCoV) poses a global threat to the swine industry.
• Understanding virus-host interactions is key to controlling viral infections.
• Limited research exists on PDCoV-host interaction factors.

Purpose of the Study:

• To identify host proteins interacting with PDCoV genomic RNA and viral proteins.
• To construct a PDCoV-host protein interaction network.
• To investigate the role of identified host factors in PDCoV replication and explore potential antiviral targets.

Main Methods:

• Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) to detect PDCoV genomic RNA interactions.
• Affinity purification mass spectrometry (AP-MS) to identify host interactors of PDCoV-encoded proteins.
• Construction and analysis of a PDCoV-host protein interaction network.

Main Results:

• Identified 671 host proteins involved in PDCoV replication, including metabolic enzymes, transcription factors, RNA-binding proteins (RBPs), and signal transduction components.
• Discovered SYNCRIP (hnRNP Q) as a novel host restriction factor that binds PDCoV N protein and blocks its degradation.
• Demonstrated that Isoforsythiaside, a SYNCRIP inhibitor, exhibits significant in vitro and in vivo antiviral activity against PDCoV.

Conclusions:

• This study provides a comprehensive resource of PDCoV-host protein interactions.
• Identified host factors and pathways offer potential targets for broad-spectrum antiviral interventions against coronaviruses.
• SYNCRIP represents a promising target for developing novel anti-PDCoV therapeutics.