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Herpes simplex virus (HSV) infection is the major cause of neonatal and sporadic encephalitis as well as genital herpes globally. Although acyclovir (ACV) and related nucleoside analogs are valuable drugs for the treatment of infection and the suppression of dissemination, HSV remains highly prevalent worldwide. The emergence of resistance to ACV has also created an obstacle for the treatment of HSV-infected immunocompromised patients and highlights the need for new, safe and effective antiviral agents. Natural products, particularly traditional medicines, which have provided multiple novel drug leads, are known to be an important source of anti-HSV agents, even though their mechanisms of action and targets are unknown. In recent years, potential targets for anti-HSV agents have been identified, and these may be the targets of the effective natural products whose mechanisms are currently unknown. This review will focus on anti-HSV herbs, extracts, fractions and compounds from natural sources, in addition to potential anti-HSV targets. By creating a summary of the characteristics of active anti-HSV compounds and using that summary to mine natural product databases, a better drug discovery paradigm may be found.
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