There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Existing options include antivirals that have been approved for clinical administration and a limited number of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown, and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. These 5CC are effective inhibitors of herpes viral DNA synthesis and interferon (IFN)-induced cellular antiviral response, and they were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. Antiviral activity of the 5CC against HSV-1 and HSV-2 was tested on RC-37 cells in vitro using a plaque reduction assay. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests comprising of a PEA, were performed to evaluate the susceptibility of HSV-1 and HSV-2 to antiherpetic drugs in Vero cells after virus entry. Indicators of the 5CC found that the combination exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. These results suggest that the 5CC are strong alternative candidates for treating herpes simplex.