Inhibition of herpes simplex type 1 and type 2 infections by Oximacro®, a cranberry extract with a high content of A-type proanthocyanidins (PACs-A)

•The cranberry extract Oximacro® has high concentration of A-type proanthocyanidins (PACs).•Oximacro® impairs in vitro HSV-1 and HSV-2 replication.•Oximacro® prevents HSV-1 and HSV-2 attachment to target cells.•Oximacro® determines alterations of envelope glicoproteins of HSV-1 and HSV-2.•Oximacro® is a promising candidate for development of new microbicides against HSV-1 and HSV-2 infections.

In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro® and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro® prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro® and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro® completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro®.Taken together, these findings indicate Oximacro® as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections.