Currently, human Herpes Simplex Virus (HSV) infection affects about 82 percent of Germany’s population. The pathogen is categorized into two types, which differ in their predilection for the site of infection. HSV type 1 (HSV-1) is associated with a wide range of clinical manifestations including cold sores. In contrast, HSV type 2 (HSV-2) is linked to genital herpes. Both types are able to develop severe disease progression leading to fatal Herpes Simplex Encephalitis (inflammation of the brain). Until now nucleoside analogues, such as Acyclovir and Valacyclovir, are still the treatment of choice for HSV infections. However, due to the existence of nucleoside-resistant viral strains alternative therapies are needed.
Recently, this alternative has been represented by helicase-primase inhibitors (HPIs), which use a novel mechanism of action to inhibit viral replication. In a drug development trial we analyzed the antiviral efficacy of new drug candidates for the treatment of HSV infections in a mouse model. The mice were infected with HSV and treated daily for five days post infection with the compounds of the novel drug class, Valacyclovir or placebo.
Despite the lower dose, we observed a better outcome in clinical parameters in comparison to Valacyclovir control. We could not observe toxic side effects during the monitoring period of 3 weeks post infection. The subsequent analysis showed that treated animals harbor a significantly lower viral load compared with placebo animals.
In this project we showed that treatment with the new development candidates can significantly reduce or prevent clinical symptoms. HPI‘s are at least one order of magnitude more potent and efficacious compared to Valacyclovir. Thus, candidates of the new drug class are promising inhibitors of HSV infections in vivo and should be translated into clinical trials.