Acyclovir, cidofovir, and amenamevir have additive antiviral effects on herpes simplex virus TYPE 1

Herpes simplex virus-1 (HSV-1) affects a large portion of the global population and has been shown to cause more severe symptoms in immunocompromised patients. It is in immunocompromised populations that HSV-1 has shown to have higher rates of resistance to the most commonly used antiherpetics, such as acyclovir/valacyclovir/penciclovir/famciclovir. The development of drug resistance has forced research into new antiherpetic therapies, including combination drug therapies. One potential complication of multidrug therapies is the existence of drug-drug interactions; as more drugs are used in the therapy, those interactions tend to become more complicated. This study tested the combination of acyclovir/cidofovir/amenamevir, the last drug being a new antiherpetic that targets the helicase-primase complex to prevent replication of viral DNA, for multidrug intervention. We used the design of experiments (DOE) function in Minitab to analyze the drug-drug interactions in their ability to inhibit growth of HSV-1. The DOE software was unable to detect any significant drug-drug interactions among these three antiherpetics as dosed. This would imply that these drugs could be used in combination to suppress viral replication without synergistic or antagonistic effects. This study shows that this therapy holds potential for further study and that DOE software is a potentially useful tool for determining complex drug-drug interactions. •The IC25 and IC50 of acyclovir, cidofovir, and amenamevir were determined against infection of cells in culture with HSV-1.•These drugs were tested in pairs and in a triple-drug combination against primary infection of HSV-1.•These three drugs were shown not to work antagonistically against each others' antiviral activity.•However, these drugs work additively in pairs and in full combination to suppress primary infection with HSV-1.