Synthesis and Bioevaluation of Chalcones as Broad-Spectrum Antiviral Compounds Against Single-Stranded RNA Viruses

Area of Science:

• Organic Chemistry
• Virology
• Medicinal Chemistry

Background:

• Chalcones are plant-derived flavonoids with diverse biological activities.
• Chalcone 8o demonstrated antiviral properties against nuclear-replicating viruses like HCMV and HIV.
• RNA viruses replicating in the cytoplasm present distinct antiviral targets.

Purpose of the Study:

• Synthesize novel chalcone derivatives based on compound 8o.
• Evaluate antiviral efficacy against four distinct families of cytoplasmic RNA viruses.
• Investigate the mechanism of action and structure-activity relationships of these chalcones.

Main Methods:

• Synthesis of ten new chalcone derivatives.
• In vitro antiviral assays against paramyxovirus, flavivirus, bunyavirus, and coronavirus.
• Cytotoxicity assessments in human fibroblast cultures.
• Time-of-addition studies to determine the stage of viral replication targeted.

Main Results:

• Chalcones 8o and 8p exhibited potent inhibition of PIV5 replication with low cytotoxicity.
• The synthesized chalcones target an early stage of viral replication, preventing viral spread.
• Significant in vitro antiviral activity was observed against Zika virus, La Crosse Virus, and coronavirus OC43.

Conclusions:

• Chalcone derivatives demonstrate broad-spectrum antiviral potential against cytoplasmic RNA viruses.
• Structural modifications of chalcone scaffolds influence antiviral efficacy.
• These findings support the development of chalcones as a promising class of broad-spectrum antiviral agents.