Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome

Area of Science:

• Virology
• Drug Discovery
• Computational Biology

Background:

• The COVID-19 pandemic highlighted the need for new therapeutic agents against SARS-CoV-2.
• Emerging virus variants necessitate continuous research into antiviral strategies.

Purpose of the Study:

• To repurpose existing drugs for inhibiting SARS-CoV-2 infection.
• To establish a high-throughput screening platform for drug discovery against SARS-CoV-2.

Main Methods:

• Screened approximately 1000 drugs in vitro for inhibition of SARS-CoV-2-induced cell death.
• Analyzed drug effects on viral nucleocapsid protein expression and determined drug targets in silico.
• Assessed drug-induced phospholipidosis and validated Duvelisib's interaction with PARP1 and the S protein.

Main Results:

• Identified Duvelisib as a potential drug targeting virus-host protein interactions through in silico analysis.
• Validated the interaction between PARP1 and the S protein, modulated by Duvelisib, using immunoprecipitation.
• Demonstrated a platform for rapid drug repurposing and evaluation against emerging viruses.

Conclusions:

• The developed platform enables efficient drug repurposing for viral infections.
• Duvelisib shows promise as a therapeutic agent by targeting key virus-host interactions.
• In silico studies can uncover druggable host pathways crucial for viral replication.