Protocol for Screening Host-Targeting Antivirals (HTAs) Using Human PBMCs and pDCs

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Host-targeting antivirals (HTAs) offer advantages over virus-targeting antivirals (VTAs) in overcoming drug resistance and providing broad-spectrum protection.
• Rapidly mutating or emerging viruses necessitate novel antiviral strategies.
• Plasmacytoid dendritic cells (pDCs) and peripheral blood mononuclear cells (PBMCs) are key producers of Type I interferons (IFNs), crucial for innate immunity.

Purpose of the Study:

• To present an optimized ex vivo protocol for screening HTAs.
• To enable the discovery of antivirals that modulate host immune responses, particularly innate immunity.
• To provide a versatile tool for testing antivirals against various viral pathogens, including emerging viruses like dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV).

Main Methods:

• Utilizes human PBMCs or pDCs for antiviral screening.
• Focuses on host immune pathways, specifically innate immunity modulation.
• Optimized for screening soluble or intravenous-formulated compounds against DENV, CHIKV, and ZIKV.

Main Results:

• The protocol enables the screening of HTAs that target host immune responses.
• It allows for species-independent antiviral activity, reducing viral escape.
• Demonstrates applicability to DENV, CHIKV, and ZIKV, building upon established methods.

Conclusions:

• This protocol offers a novel avenue for HTA discovery by focusing on pDC-mediated immune modulation.
• It serves as an essential resource for pandemic preparedness and broad-spectrum antiviral research.
• The method is suitable for evaluating antiviral efficacy in experimental settings.