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Acyclovir and Epstein-Barr virus infection
Abstract:
Acyclovir (ACV) has an ED50 of 0.3 microM against EBV replication in vitro. Based on these and other data we carried out a pilot, double-blind, placebo-controlled trial of ACV for treatment of infectious mononucleosis. Only patients with relatively severe illness requiring hospital management were enrolled. Ten subjects with proven infectious mononucleosis received placebo and 10 ACV. The drug was administered intravenously at 8-hourly intervals in a total daily dosage of 1500 mg/m2 for 5 days. Preliminary analyses of the results indicate that the drug interrupted virus excretion in the oropharynx transiently but had no effect on ability to generate lymphocytic lines from peripheral blood. Symptoms and signs unaffected by ACV were splenomegaly, lymphadenopathy, lethargy, fever and pharyngitis. There was significantly more rapid regain of weight in the ACV-treated group. On the basis of these results we have instituted an out-patient trial of orally administered ACV in patients with less severe illness earlier in its course. We have also begun in-vitro tests of other drugs that might prove to be effective against Epstein-Barr virus infection, and have shown that 9-1 (1,3-dihydroxy-2-propoxymethyl)guanine (BW759) has an ED50 of 0.05 microM.
Insights
Acyclovir (ACV) showed transient effects on Epstein-Barr virus (EBV) shedding in severe infectious mononucleosis patients but did not improve most symptoms. However, ACV did lead to faster weight regain in treated individuals.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Epstein-Barr virus (EBV) causes infectious mononucleosis.
- Acyclovir (ACV) demonstrates in vitro activity against EBV replication.
- Limited data exists on ACV efficacy for treating infectious mononucleosis.
Purpose of the Study:
- To evaluate the efficacy of intravenous acyclovir (ACV) in hospitalized patients with severe infectious mononucleosis.
- To assess ACV's impact on viral shedding, immune response, and clinical symptoms.
Main Methods:
- Pilot, double-blind, placebo-controlled trial.
- Ten severe infectious mononucleosis patients received placebo, ten received ACV (1500 mg/m2 daily IV for 5 days).
- Evaluated viral excretion, lymphocyte generation, and clinical signs/symptoms.
Main Results:
- ACV transiently interrupted oropharyngeal EBV shedding.
- No significant effect on lymphocyte generation, splenomegaly, lymphadenopathy, lethargy, fever, or pharyngitis.
- ACV-treated group showed significantly faster weight regain.
- BW759, another drug, showed potent in vitro activity (ED50 of 0.05 microM).
Conclusions:
- Intravenous ACV has limited clinical benefit for severe infectious mononucleosis, despite transiently reducing viral shedding.
- Further investigation into oral ACV for milder, earlier-stage illness is warranted.
- Exploration of alternative antivirals like BW759 for EBV infections is ongoing.