Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle.

• Keywords
• HSV latency, acyclovir resistance, antiviral mechanisms, herpes simplex virus, herpesvirus infections, natural antivirals, phenolic acids, polyphenols, synergistic antiviral effects, tannins,
• MeSH
• Antiviral Agents * pharmacology   therapeutic use   chemistry   MeSH
• Herpes Simplex * drug therapy   virology   MeSH
• Hydroxybenzoates * pharmacology   chemistry   therapeutic use   MeSH
• Humans MeSH
• Herpesvirus 1, Human * drug effects   physiology   MeSH
• Herpesvirus 2, Human drug effects   MeSH
• Virus Replication drug effects   MeSH
• Simplexvirus * drug effects   physiology   MeSH
• Tannins * pharmacology   chemistry   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antiviral Agents * MeSH
• Hydroxybenzoates * MeSH
• phenolic acid MeSH Browser
• Tannins * MeSH

The Epstein-Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors.

• Keywords
• EBV life cycle, EBV-associated cancers, Epstein–Barr virus, anticancer effects, antiviral properties, flavones, flavonoids, flavonols, host–EBV interaction, viral and cellular genes, viral and cellular proteins,
• MeSH
• Antiviral Agents * pharmacology   therapeutic use   chemistry   MeSH
• Flavonols * pharmacology   therapeutic use   chemistry   MeSH
• Flavones * pharmacology   therapeutic use   chemistry   MeSH
• Epstein-Barr Virus Infections * drug therapy   complications   virology   MeSH
• Humans MeSH
• Neoplasms * drug therapy   virology   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Herpesvirus 4, Human * drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antiviral Agents * MeSH
• Flavonols * MeSH
• Flavones * MeSH
• Antineoplastic Agents MeSH

Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt's lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.

• Keywords
• Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), anticancer properties, antiviral activities, cancer treatment, carcinogenesis, flavonoids, herpesviruses, molecular mechanisms, tumor viruses,
• MeSH
• Anthocyanins MeSH
• Flavonoids pharmacology   therapeutic use   MeSH
• Herpesviridae * MeSH
• Epstein-Barr Virus Infections * drug therapy   MeSH
• Sarcoma, Kaposi * pathology   MeSH
• Carcinogenesis MeSH
• Humans MeSH
• Herpesvirus 8, Human * genetics   MeSH
• Neoplasms * drug therapy   MeSH
• Herpesvirus 4, Human genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Anthocyanins MeSH
• Flavonoids MeSH