title: Poly (4-styrenesulfonic acid-co-maleic acid) is an entry inhibitor against both HIV-1 and HSV infections - potential as a dual functional microbicide.
abstract: Genital herpes is one of the most prevalent sexually transmitted diseases (STD) caused by herpes simplex viruses type 1 and 2 (HSV-1 and -2). HSV is considered as a major risk factor in human immunodeficiency virus type-1 (HIV-1) infection and rapid progression to acquired immunodeficiency syndrome (AIDS). Here, we reported the finding of a polymer of styrenesulfonic acid and maleic acid (PSM) which exhibited antiviral activity with low cytotoxicity. PSM exhibited in vitro inhibitory activity against HIV-1 pseudovirus and HSV-1 and -2. In vivo efficacy of PSM against HSV-2 (G) was also investigated. We found that both 1% and 5% PSM gels protected mice from HSV-2 vaginal infection and disease progression significantly. Mechanistic analysis demonstrated that PSM was likely an entry inhibitor that disrupted viral attachment to the target cells. In particular, PSM disrupted gp120 binding to CD4 by interacting with the gp120 V3-loop and the CD4-binding site. The in vitro cytotoxicity studies showed that PSM did not stimulate NF-κB activation and up-regulation of proinflammatory cytokine IL-1β and IL-8 in vaginal epithelial cells. In addition, PSM also showed low adverse effect on the growth of vaginal Lactobacillus strains. PSM is, therefore, a novel viral entry inhibitor and a potential microbicide candidate against both HIV-1 and HSV.
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Qiu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Siwei
authors.initials: S
authors.lastname: Song
authors.forename: Hongyong
authors.initials: H
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Chu
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Yuan
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Datong
authors.initials: D
authors.lastname: Zheng
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008298:Maleates / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D011137:Polystyrenes / Q000008:administration & dosage*; D015229:Sexually Transmitted Diseases, Viral / Q000517:prevention & control; D016896:Treatment Outcome; D014621:Vagina / Q000382:microbiology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D008298:Maleates; D011137:Polystyrenes; D014622:Vaginal Creams, Foams, and Jellies; C518261:poly(4-styrenesulfonic acid-co-maleic acid)