In vitro antiviral activity of aphidicolin and its derivates. Synergistic effects of aphidicolin with other antiviral drugs.
Twenty derivatives of aphidicolin were tested against HSV (herpes simplex virus), HCMV (human cytomegalovirus) and adenovirus in vitro. In addition, the antiviral activity of aphidicolin (CAS 38966-21-1) in combination with aciclovir (CAS 59277-89-3) or cidofovir (CAS 113852-37-2) against HSV was determined. The antiviral effects were evaluated using plaque reduction assay in Vero cells or human Foreskin Fibroblasts (HFF) for HSV and HCMV, respectively. Combination indexes were calculated using the method of Chou and Talalay. Two derivatives (K14254 and K14266) that are considered to be prodrugs of aphidicolin were shown to inhibit HCMV and HSV replication comparably to aphidicolin. None of the tested substances inhibited adenovirus replication. Aphidicolin acted synergistically with aciclovir in a 1:1 molar ratio and with cidofovir in different ratios. Aphidicolin and its two antiviral active derivatives might represent useful additional tools for antiviral therapy of HSV and HCMV infections, especially in combination with clinically used drugs.
Michaelis
Martin
M
Institut für Medizinische Virologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Langer
Klaus
K
Vogel
Jens-Uwe
JU
Kreuter
Jörg
J
Rabenau
Holger
H
Doerr
Hans-Wilhelm
HW
Cinatl
Jindrich
J
D000256:Adenoviridae / Q000187:drug effects; D000998:Antiviral Agents / Q000494:pharmacology*; D016590:Aphidicolin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007202:Indicators and Reagents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D016590:Aphidicolin; D003596:Cytosine; D000077404:Cidofovir