Abstract
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.
Highlights
Herpes simplex virus infections are considered a major public health issue worldwide.These human pathogen DNA viruses belong to the family of Alphaherpesvirinae
It was important roles regulating β and γ gene expression, which is needed for Herpes simplex viruses (HSV)-1 replication uncovered to inactivate herpes simplex virus type 1 (HSV-1) DNA-polymerase, which catalyzes the synthesis of DNA
The process by which HSV attaches to the cell surface and enters the cell is mediated by different glycoproteins on the surface of the virus
Summary
Herpes simplex virus infections are considered a major public health issue worldwide. Many different antiviral drugs targeting the viral DNA-polymerase were approved for the treatment of acute HSV infections. Resistance emerges against drugs such as famciclovir or penciclovir that target HSV-TK and against the viral DNA-polymerase inhibitors foscarnet and cidofovir [14], the latter severely in patients undergoing stem cell transplantation [12]. DNA-polymerase inhibitors can be used for the treatment of ACV-resistant HSV infections Their use is limited due to possible serious side effects, especially in patients with comorbidities [5]. We focused on wellcharacterized compounds with already uncovered mechanisms of how these compounds interfere with the viral replication This strategy allows for conclusions about the potential antiviral activity of these compounds against ACV-resistant viruses. The review gives an overview of the distinct compounds isolated from plants and other natural sources and summarizes the results from in vitro and in vivo studies conducted far
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