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

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.