SARS-CoV-2-host proteome interactions for antiviral drug discovery

Area of Science:

• Virology
• Molecular Biology
• Drug Discovery

Background:

• Limited treatment options for COVID-19 necessitate understanding SARS-CoV-2 pathogenesis.
• Host-viral interactions are crucial for viral replication and therapeutic target identification.

Purpose of the Study:

• To construct a comprehensive network of SARS-CoV-2-host interactions.
• To identify critical host machineries for viral processing.
• To discover potential drug repurposing candidates for COVID-19 treatment.

Main Methods:

• Affinity purification mass spectrometry (AP-MS) and proximity-based labeling (BioID-MS) were used to map interactions.
• 29 viral ORFs and 18 host proteins were analyzed.
• Virtual screening was employed for drug repurposing.

Main Results:

• A network of 693 hub proteins interacting with both viral and host factors was identified.
• 59 compounds were suggested for repurposing against 15 protein targets.
• In vitro validation confirmed antiviral effects of candidate drugs, including methotrexate.

Conclusions:

• The study provides a valuable resource for understanding SARS-CoV-2-host interactions.
• Drug repurposing based on interactome analysis shows promise for COVID-19 therapy.
• Methotrexate's antiviral activity may stem from inhibiting specific protein-protein interactions.