More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term
latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against
latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to
acyclovir and related
nucleoside analogues can occur when mutations arise in either HSV
thymidine kinase or
DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential
herbal medicines. One example is
Glycyrrhizic acid isolated from licorice that shows promising
antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While
nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus
latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral
infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent
herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with
nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral
therapies.