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Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication
J C Lin1, E DeClercq, J S Pagano
1Lineberger Cancer Research Center, School of Medicine, University of North Carolina Chapel Hill 27514.
Antimicrobial Agents and Chemotherapy
|September 1, 1987
Summary
Two acyclic adenosine analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), show potent anti-Epstein-Barr virus (EBV) activity. These selective agents inhibit EBV replication in vitro without significant cellular toxicity.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Epstein-Barr virus (EBV) is a human herpesvirus associated with various malignancies.
- Development of effective antiviral agents against EBV is crucial for therapeutic intervention.
Purpose of the Study:
- To evaluate the in vitro efficacy of three novel acyclic adenosine analogs against Epstein-Barr virus (EBV) replication.
- To assess the selectivity and potency of these compounds as potential anti-EBV agents.
Main Methods:
- Testing of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] in EBV-infected cell lines.
- Quantification of EBV DNA replication using cRNA-DNA hybridization and density gradient centrifugation.
- Determination of 50% effective doses (ED50) and assessment of cellular cytotoxicity.
Main Results:
- Both (S)-HPMPA and PMEA demonstrated significant inhibition of EBV DNA replication.
- (S)-HPMPA and PMEA exhibited ED50 values of 0.08 microM and 1.1 microM, respectively.
- The compounds were cytostatic but not cytotoxic at concentrations up to 100 microM, indicating high selectivity.
Conclusions:
- (S)-HPMPA and PMEA are potent and selective antiviral agents against Epstein-Barr virus in vitro.
- These acyclic adenosine analogs represent promising candidates for further development as anti-EBV therapies.