A High-Throughput Flow Cytometry Screen Identifies Molecules That Inhibit Hantavirus Cell Entry

Area of Science:

• Virology
• Drug Discovery
• Immunology

Background:

• Hantaviruses cause severe diseases like hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS).
• Sin Nombre virus (SNV) and Andes virus (ANDV) are major causes of HCPS, with high fatality rates.
• No specific antiviral therapies or vaccines currently exist for SNV.

Purpose of the Study:

• To screen for small-molecule inhibitors targeting the interaction between hantaviruses and host cells.
• To identify novel compounds that can inhibit SNV and other HCPS-causing viruses.
• To validate the efficacy and mechanism of action of identified inhibitors.

Main Methods:

• High-throughput flow cytometry was used to screen the Prestwick Chemical Library.
• The screen focused on inhibitors of the binding between UV-inactivated SNV particles and decay-accelerating factor (DAF).
• Hit compounds underwent secondary screening for infection inhibition, cytotoxicity, and probe interference, followed by orthogonal testing.

Main Results:

• Antimycin was identified as a potent inhibitor of cellular infection by SNV and Hantaan virus.
• Orthogonal testing confirmed that antimycin directly binds to the virus particle.
• The compound was shown to block virus-mediated integrin activation, a key step in cellular infection.

Conclusions:

• Antimycin is a promising candidate for the development of novel therapies against HCPS.
• The study validates a screening approach for identifying hantavirus inhibitors.
• Understanding the mechanism of viral entry provides targets for future therapeutic interventions.