Structural evidence of quercetin multi-target bioactivity: A reverse virtual screening strategy

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Quercetin, a widely studied flavonoid, exhibits significant anti-cancer, anti-inflammatory, and cytoprotective properties.
• Its therapeutic benefits are often attributed to direct antioxidant activity, but interactions with cellular targets and signaling pathways are increasingly recognized.
• A comprehensive understanding of quercetin's molecular targets and mechanisms of action remains incomplete.

Purpose of the Study:

• To identify novel protein targets of quercetin using computational screening methods.
• To elucidate the potential mechanisms underlying quercetin's pleiotropic effects.
• To support the therapeutic potential of quercetin in various diseases.

Main Methods:

• Employed a reverse screening strategy combining ligand similarity (SHAFTS) and target structure (idTarget, LIBRA).
• Predicted a set of potential protein targets for quercetin.
• Validated the screening approach by corroborating previously identified targets.

Main Results:

• Identified protein kinases and poly [ADP-ribose] polymerases as major target families for quercetin.
• Discovered that predicted targets are involved in key signaling pathways, suggesting multilevel interactions.
• Confirmed the suitability of the computational screening approach for target identification.

Conclusions:

• Quercetin possesses a broad target profile, impacting multiple signaling pathways.
• This extensive target engagement supports a pleiotropic, multilevel, and potentially synergistic mechanism of action.
• Quercetin's complex molecular interactions highlight its therapeutic value for inflammation, neurodegeneration, and cancer.