title: Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry.
abstract: Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum and mechanism of antiviral activity were explored using clinical isolates and laboratory-adapted strains of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). SAMMA is highly effective against all CCR5 and CXCR4 isolates of HIV in primary human macrophages and peripheral blood mononuclear cells. SAMMA also inhibits infection of cervical epithelial cells by HSV. Moreover, it exhibits little or no cytotoxicity and has an excellent selectivity index. SAMMA, although not a sulfonated or sulfated polymer, blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and also inhibits HSV entry postattachment. SAMMA is an excellent, structurally novel candidate microbicide that warrants further preclinical evaluation.
authors.affiliation: Departments of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA. betsy.herold@mssn.edu
authors.forename: B C
authors.initials: BC
authors.lastname: Herold
authors.forename: I
authors.initials: I
authors.lastname: Scordi-Bello
authors.forename: N
authors.initials: N
authors.lastname: Cheshenko
authors.forename: D
authors.initials: D
authors.lastname: Marcellino
authors.forename: M
authors.initials: M
authors.lastname: Dzuzelewski
authors.forename: F
authors.initials: F
authors.lastname: Francois
authors.forename: R
authors.initials: R
authors.lastname: Morin
authors.forename: V Mas
authors.initials: VM
authors.lastname: Casullo
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
authors.forename: C
authors.initials: C
authors.lastname: Chany
authors.forename: D P
authors.initials: DP
authors.lastname: Waller
authors.forename: L J D
authors.initials: LJ
authors.lastname: Zaneveld
authors.forename: M E
authors.initials: ME
authors.lastname: Klotman
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity*; D006561:Herpes Simplex / Q000517:prevention & control; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008333:Mandelic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000494:pharmacology* / Q000633:toxicity; D018139:Simplexvirus / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity*
chemical_list: D000998:Antiviral Agents; D008333:Mandelic Acids; D011108:Polymers; C037938:mandelic acid