Inhibition of Herpes Simplex Virus Type 1 and 2 In Vitro Infection by Sulfated Derivatives of K5 Escherichia coli Polysaccharide

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are neurotropic viruses and common human pathogens causing a major public health problem such as genital herpes, a sexually transmitted disease also correlated to increased transmission and replication of the 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 vs. molecules acting selectively against either infection. We here report that sulfated derivatives of the Escherichia coli K5 polysaccharide, structurally highly similar to heparin and previously shown to inhibit in vitro HIV-1 entry and replication, also exert suppressive activities against both HSV-1 and HSV-2 infections. In particular, the N, O-sulfated [K5-N,OS(H)] and the O-sulfated epimerized form [Epi-K5-OS(H)] inhibited HSV-1 and 2 infection of Vero cells and their 50% inhibitory concentration (IC50) was between 3 ± 0.05 and 48 ± 27 nM while not being toxic to the cells at concentrations up to 5 μM. These compounds impaired the early steps of HSV-1 and HSV-2 virion attachment and entry into host cells and reduced 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 their development as topical microbicides preventing sexual transmission of HIV-1, HSV-1 and HSV-2. AC CE PT ED on O cber 5, 2017 by gest httpaac.asm .rg/ D ow nladed fom