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Antimicrobial Agents and Chemotherapy, September 2008, p. 3078-3084, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00359-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of Herpes Simplex Virus Types 1 and 2 In Vitro Infection by Sulfated Derivatives of Escherichia coli K5 Polysaccharide{triangledown}

Debora Pinna,1 Pasqua Oreste,2 Tiziana Coradin,1 Anna Kajaste-Rudnitski,1 Silvia Ghezzi,1 Giorgio Zoppetti,2 Antonella Rotola,3 Rafaela Argnani,3 Guido Poli,4,5 Roberto Manservigi,3 and Elisa Vicenzi1*

Viral Pathogens and Biosafety Unit,1 AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute,4 Glycores 2000 S.r.l,2 Vita-Salute San Raffaele University, School of Medicine, Milan,5 Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Ferrara, Italy3

Received 14 March 2008/ Returned for modification 2 April 2008/ Accepted 13 June 2008

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 (IC50) between 3 ± 0.05 and 48 ± 27 nM, and were not toxic to the cells at concentrations as high as 5 µM. 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.

* Corresponding author. Mailing address: P2-P3 Laboratories DIBIT, Via Olgettina 58, 20132, Milan, Italy. Phone: 39-02-2643-4908. E-mail: vicenzi.elisa{at}hsr.it

{triangledown} Published ahead of print on 23 June 2008.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3078-3084, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00359-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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