Antiviral and immunomodulatory activity of the metal chelator ethylenediaminedisuccinic acid against cytomegalovirus in vitro and in vivo.
Antiviral activity of the metal chelator ethylenediaminedisuccinic acid (EDDS) was examined in vitro against human cytomegalovirus (HCMV) wild type strains and strains that are resistant against ganciclovir (GCV) and cidofovir (HPMPC). EDDS inhibited the replication of wild-type as well as GCV- and HPMPC-resistant strains with a 50% effective concentration of 7.4-12 microg/ml. At concentrations of 100 microg/ml EDDS, unlike GCV or HPMPC, suppressed HCMV-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) and reduced T-cell adhesion to HCMV-infected cells in a monolayer adhesion model. In vitro EDDS inhibited murine cytomegalovirus (MCMV) replication (EC50 8.6 microg/ml) and caused in mice some protection against MCMV induced mortality at a non-toxic dose. Since immunopathological factors may play a significant role in HCMV disease it will be of interest to further study whether EDDS is effective in terms of modulation of inflammatory responses to HCMV infections.
Vogel
J-U
JU
Institut für Medizinische Virologie, Klinikum der Johann Wolfgang Goethe-Universität, Paul-Ehrlich-Str. 40, D-60596 a. M., Frankfurt, Germany. j.vogel@em.uni-frankfurt.de
Michaelis
M
M
Neyts
J
J
Blaheta
R A
RA
Snoeck
R
R
Andrei
G
G
De Clercq
E
E
Rabenau
H F
HF
Kreuter
J
J
Cinatl
J
J
Doerr
H W
HW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005029:Ethylenediamines / Q000494:pharmacology*; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D016513:Mice, SCID; D018146:Muromegalovirus / Q000187:drug effects; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D002614:Chelating Agents; D005029:Ethylenediamines; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D013386:Succinates; D018799:Intercellular Adhesion Molecule-1; C041447:N,N'-ethylenediamine disuccinic acid; D003596:Cytosine; D000077404:Cidofovir