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).
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.
Microbiology and Virology Unit, Department of Life Science and Systems Biology, University of Turin, 10123 Turin, Italy. Electronic address: mariaelena.terlizzi@unito.it.
Maria Elena
ME
Terlizzi
Plant Physiology Unit, Department of Life Science and Systems Biology, University of Turin, 10123 Turin, Italy; Biosfered S.r.l., 10135 Turin, Italy. Electronic address: andrea.occhipinti@unito.it.
Andrea
A
Occhipinti
Microbiology and Virology Unit, Department of Life Science and Systems Biology, University of Turin, 10123 Turin, Italy. Electronic address: anna.luganini@unito.it.
Anna
A
Luganini
Plant Physiology Unit, Department of Life Science and Systems Biology, University of Turin, 10123 Turin, Italy; Biosfered S.r.l., 10135 Turin, Italy. Electronic address: massimo.maffei@unito.it.
Massimo E
ME
Maffei
Microbiology and Virology Unit, Department of Life Science and Systems Biology, University of Turin, 10123 Turin, Italy. Electronic address: giorgio.gribaudo@unito.it.
Giorgio
G
Gribaudo
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D010936:Plant Extracts; D044945:Proanthocyanidins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins
A-type proanthocyanidins; Antiviral activity; Herpes simplex virus 1; Herpes simplex virus 2; Microbicides; Vaccinium macrocarpon (cranberry) extract