Antiviral Drug Therapy of Filovirus Infections: S-Adenosylhomocysteine Hydrolase Inhibitors Inhibit Ebola Virus In Vitro and in a Lethal Mouse Model

Ebola (subtype Zaire) viral replication was inhibited in vitro by a series of nine nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase, an important target for antiviral drug development. Adult BALB/c mice lethally infected with mouse-adapted Ebola virus die 5–7 days after infection....

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Bibliographic Details
Published in:The Journal of infectious diseases 1999-02, Vol.179 (Supplement-1), p.S240-S247
Main Authors: Huggins, John, Zhang, Zhen-Xi, Bray, Mike
Format: Article
Language:English
Subjects:
Adenosylhomocysteinase
Animals
Antiviral Agents - chemistry
Antiviral Agents - therapeutic use
Antivirals
Cercopithecus aethiops
Disease Models, Animal
Dosage
Drug design
Drug Evaluation
Drug Evaluation, Preclinical
Ebola virus
Ebolavirus - drug effects
Ebolavirus - pathogenicity
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - therapeutic use
Enzymes
Experimental Therapy
Hemorrhagic Fever, Ebola - drug therapy
Hemorrhagic Fever, Ebola - virology
Hydrolases - antagonists & inhibitors
In Vitro Techniques
Infections
Liver
Liver - virology
Mice
Mice, Inbred BALB C
Primates
Spleen - virology
Time Factors
Tubercidin - analogs & derivatives
Tubercidin - therapeutic use
Vero Cells
Viruses
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Summary:Ebola (subtype Zaire) viral replication was inhibited in vitro by a series of nine nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase, an important target for antiviral drug development. Adult BALB/c mice lethally infected with mouse-adapted Ebola virus die 5–7 days after infection. Treatment initiated on day 0 or 1 resulted in dose-dependent protection, with mortality completely prevented at doses ⩾0.7 mg/kg every 8 h. There was significant protection (90%) when treatment was begun on day 2, at which time, the liver had an average titer of 3 × 105 pfu/g virus and the spleen had 2 × 106 pfu/g. Treatment with 2.2 mg/kg initiated on day 3, when the liver had an average titer of 2 × 107 pfu/g virus and the spleen had 2 × 108 pfu/g, resulted in 40% survival. As reported here, Carbocyclic 3-deazaadenosine is the first compound demonstrated to cure animals from this otherwise lethal Ebola virus infection.
ISSN:0022-1899
1537-6613
DOI:10.1086/514316