Natural products and dietary bioactives as antiviral agents against herpesviruses: molecular mechanisms, immunomodulatory actions, and nutritional perspectives.

Herpesvirus infections, including HSV-1, HSV-2, VZV, EBV, CMV, and HHV-6–8, affect billions globally and pose major health challenges due to their ability to establish lifelong latency and periodic reactivation. Current antiviral therapies, such as acyclovir and related nucleoside analogs, are effective for acute infections but limited by drug resistance, toxicity, and inability to eradicate latent virus. Natural products and dietary bioactive have emerged as promising alternatives or adjuncts due to their broad-spectrum antiviral, immunomodulatory, and anti-inflammatory activities. Bioactive compounds such as polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, peptides, and micronutrients interfere with multiple stages of the herpesvirus life cycle, including viral attachment, entry, replication, and assembly, while influencing latency and host gene regulation. These agents also enhance host defense by modulating cytokine signaling, activating natural killer cells and macrophages, and reducing oxidative and inflammatory stress. Additionally, nutritional and microbiota-mediated pathways through functional foods, probiotics, and micronutrients like vitamins C and D, zinc, and selenium support immune resilience and antiviral activity. Emerging computational and omics-based tools, including molecular docking, metabolomics, network pharmacology, and artificial intelligence, have further clarified the molecular targets of these bioactives.