<i>In vitro</i> activity of Cacicol^® on herpes simplex virus type 1: a promising adjunct therapy of herpetic corneal infections?

Purpose Herpes simplex keratitis (HSK) remains the leading cause of infectious blindness in developed countries. Cacicol ® , a topical eye biopolymer containing a poly‐carboxymethyl sulfate solution is a recent licensed regenerating agent used for matrix repair therapy, intended for wound healing of corneal epithelial defects. According to its chemical composition, we hypothesized that Cacicol ® could compete with natural heparan sulfate which initiates cell surface attachment of herpes simplex virus type 1 (HSV‐1) and that Cacicol ® could have unexplored antiherpetic activities. Methods Cacicol ® was tested in vitro against both cell free HSV‐1 SC16 strain and HSV‐1 PSL‐R, a clinical isolate resistant to both acyclovir and foscarnet due to mutations in both thymidine kinase and DNA polymerase, and compared to the activity of vehicle, equivalent to active drug minus the active component. The reduction of the initial viral inoculum by Cacicol ® or vehicle, during 1 h adsorption was determined by plaque reduction assays on Vero cells. Results A dose dependent effect was demonstrated when both SC16 and PSL‐R were pre‐treated with Cacicol ® during adsorption. Initial inoculums of 1,104 PFU were significantly decreased to 160 PFU (±26.6) and 117 PFU (±22.3) for SC16 and PSL‐R respectively, while vehicle has no effect on viral replication. Conclusions Cacicol ® has a significant in vitro antiherpetic activity and seems particularly interesting for the management of HSV‐1 resistant to acyclovir or foscarnet, especially in tissues that can receive Cacicol ® by topical application (such as the cornea). Clinical studies are necessary to determine its in vivo activity and its usefulness as a promising adjunct or alternative therapy of recurrent HSK.