Abstract
Herpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant
disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral
reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains
unaffected within patients.
Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing
two classic herpes in vivo latency/reactivation animal models (intravaginal guinea pig HSV-2 infection model and
ocular mouse HSV-1 infection model) is presented. Intermittent therapy of infected animals with 4–7 cycles of
IM-250 during latency silences subsequent recurrences analyzed up to 6 months. In contrast to common expe
rience, our studies show that the latent reservoir is indeed accessible to antiviral therapy altering the latent viral
reservoir such that reactivation frequency can be reduced significantly by prior IM-250 treatment.
We provide evidence that antiviral treatment during HSV latency can reduce future reactivation from the
latent reservoir, supporting a conceptual shift in the antiviral field, and reframing what is achievable with respect
to therapy of latent neuronal HSV infections.