Thymoquinone and Its Nanoformulation for Dual Antiviral Therapy: Targeting Intracellular Viral Replication and Host...

Viral therapy requires effective control of intracellular viral replication while limiting harmful host responses that may contribute to disease progression and complications. Thymoquinone (TQ), a major bioactive constituent of Nigella sativa, has potential antiviral and host-protective properties, but its therapeutic implications are limited by poor aqueous solubility, chemical instability, and variable tissue exposure. This review critically explores TQ nanoformulations (Nano-TQ) as a promising strategy to overcome these limitations and enable dual antiviral therapy through improved intracellular delivery and modulation of virus-associated host injury. Research published between 2000 and 2026 is evaluated, with emphasis on TQ-specific antiviral activity, nanoformulation platforms, intracellular trafficking, virus-informed delivery, host complications, and translational development. Current evidence indicates that nanoformulation can improve the pharmaceutical and pharmacokinetic properties of TQ and may facilitate delivery to disease-relevant tissues. However, direct evidence that Nano-TQ can achieve functionally relevant intracellular delivery, selectively engage virus-related targets, or provide superior antiviral efficacy over free TQ remains limited. We therefore propose that the key translational benchmark should be a reproducible therapeutic advantage coupled to intracellular TQ exposure, target engagement, and reduced infectious viral output rather than improved bioavailability alone. Future studies should integrate virus-specific infection models, PK-PD relationships, and safety assessments to progress Nano-TQ toward a clinically relevant dual-action antiviral nanomedicine.