Inhibition of herpes simplex virus types 1 and 2 in vitro infection by sulfated derivatives of Escherichia coli K5 polysaccharide.
Herpes simplex virus type 1 (HSV-1) and HSV-2 are neurotropic viruses and common human pathogens causing major public health problems such as genital herpes, a sexually transmitted disease also correlated with increased transmission and replication of human immunodeficiency virus type 1 (HIV-1). Therefore, compounds capable of blocking HIV-1, HSV-1, and HSV-2 transmission represent candidate microbicides with a potential added value over that of molecules acting selectively against either infection. We report here that sulfated derivatives of the Escherichia coli K5 polysaccharide, structurally highly similar to heparin and previously shown to inhibit HIV-1 entry and replication in vitro, also exert suppressive activities against both HSV-1 and HSV-2 infections. In particular, the N,O-sulfated [K5-N,OS(H)] and O-sulfated epimerized [Epi-K5-OS(H)] forms inhibited the infection of Vero cells by HSV-1 and -2, with 50% inhibitory concentrations (IC(50)) between 3 +/- 0.05 and 48 +/- 27 nM, and were not toxic to the cells at concentrations as high as 5 muM. These compounds impaired the early steps of HSV-1 and HSV-2 virion attachment and entry into host cells and reduced the cell-to-cell spread of HSV-2. Since K5-N,OS(H) and Epi-K5-OS(H) also inhibit HIV-1 infection, they may represent valid candidates for development as topical microbicides preventing sexual transmission of HIV-1, HSV-1, and HSV-2.
Viral Pathogens and Biosafety Unit, Vita-Salute San Raffaele University, School of Medicine, Milan, Italy.
Debora
D
Pinna
Pasqua
P
Oreste
Tiziana
T
Coradin
Anna
A
Kajaste-Rudnitski
Silvia
S
Ghezzi
Giorgio
G
Zoppetti
Antonella
A
Rotola
Rafaela
R
Argnani
Guido
G
Poli
Roberto
R
Manservigi
Elisa
E
Vicenzi
D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000821:virology*; D004926:Escherichia coli / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D011995:Recombination, Genetic; D013431:Sulfates / Q000378:metabolism / Q000494:pharmacology*; D014709:Vero Cells
D013431:Sulfates; C050673:capsular polysaccharide K5