In vitro and in vivo anti-herpes simplex virus activity of monogalactosyl diacylglyceride from Coccomyxa sp. KJ (IPOD FERM BP-22254), a green microalga.

Kyoko Hayashi,Tamaki Shibayama,Kinya Atsumi,Toshio Kawahara,Jung-Bum Lee,Kazumasa Okamoto,Mana Kanazashi,Toshimitsu Hayashi,Luis M Schang

doi:10.1371/journal.pone.0219305

Abstract

A monogalactosyl diacylglyceride (MGDG) was isolated as an antiviral component from Coccomyxa sp. KJ (IPOD FERM BP-22254) via bioassay-guided fractionation. α-Linolenic acid (C18:3) and 7,10,13-hexadecatrienoic acid (C16:3) accounted for approximately 72% and 23%, respectively, of the MGDG total fatty acids of the MGDG. The MGDG showed virucidal activity against herpes simplex virus type 2 (HSV-2), a pathogen that causes genital herpes. Physical changes in HSV-2 shape were observed after treatment with MGDG, including a decrease in particle size, and possible damage to the viral envelope, as assessed using electron microscopy. In accordance with the morphological findings, virus particles lost their ability to bind to host cells. HSV-2 treated with high concentrations of MGDG resulted in no pathogenicity in an animal model, indicating that MGDG exhibits irreversible virucidal activity against HSV-2 particles. In the animal model of HSV-2-induced genital herpes, intravaginally administered MGDG exerted a prophylactic effect by suppressing viral yields in the genital cavity and formation of herpetic lesions, resulting in a higher survival rate in treated mice than control mice administered solvent. Thus, MGDG offers a novel prophylactic option against HSV infections.

Highlights

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) primarily infect epithelial tissues before spreading to the nervous system, causing lifelong infection in the sacral ganglia
These data agree with our results of binding assay of monogalactosyl diacylglyceride (MGDG)-treated virus and electron microscopy assessment, which revealed that treatment of herpes simplex virus type 2 (HSV-2) virions with MGDG resulted in lysis of virus particles
Mature virions vary in size from 120 nm to as large as 260 nm [20], which approximately agrees with our electron microscopy assessment showing that the diameter of mock-treated HSV-2 particles was around 300 nm (Fig 4)

Summary

Introduction

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) primarily infect epithelial tissues before spreading to the nervous system, causing lifelong infection in the sacral ganglia. Genital herpes caused by HSV is a common sexually transmitted infection among populations worldwide [1,2]. In vitro and in vivo anti-herpes simplex virus activity of monogalactosyl diacylglyceride from green microalga collection and analysis, decision to publish, or preparation of the manuscript. HSV strains that are resistant to nucleoside analogs, including ACV, have emerged [9], resulting in a need for development of novel anti-herpes drugs with a different mode of action from that of the nucleoside analogs. A monogalactosyl diacylglyceride (MGDG) was found to have anti-HSV properties. MGDGs with unknown chemical structures isolated from Clinacanthus nutans, a Thai herbal medicine, reportedly have anti-HSV activity in vitro [18]. We assessed the virucidal activity of MGDG, isolated from Coccomyxa sp. KJ, for its virucidal activity against HSV-2, and further elucidated its mechanism of action

Materials and methods

Result

Findings

Discussion