Herpes simplex viruses (HSV) are ubiquitously distributed with a seroprevalence ranging up to 95% in the adult population. Refractory viral infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent a major global health issue. In particular, the increasing occurrence of resistance to conventional antiviral drugs make the therapy of such infections even more challenging. For instance, the frequent and long-term use of acyclovir and other nucleoside analogues targeting the viral DNA-polymerase enhance the development of resistant viruses. Particularly, the incidental increase of those strains in immunocompromised patients is alarming and represent a major health concern. Alternative treatment concepts are clearly needed. Natural products such as herbal medicines showed antiherpetic activity in vitro and in vivo and proved to be an excellent source for the discovery and isolation of novel antivirals. By this means, numerous plant-derived compounds with antiviral or antimicrobial activity could be isolated. Natural medicines and their ingredients are well-tolerated and could be a good alternative for treating herpes simplex virus infections. This review provides an overview of the recent status of natural sources such as plants, bacteria, fungi, and their ingredients with antiviral activity against herpes simplex viruses. Furthermore, we highlight the most potent herbal medicines and ingredients as promising candidates for clinical investigation and give an overview about the most important drug classes along with their potential antiviral mechanisms. The content of this review is based on articles that were published between 1996 and 2021.
Keywords: antiherpetic drugs; herpes simplex viruses; natural products; resistance.