Synergistic Inhibition of Anatid Herpesvirus Replication by Acyclovir and Phosphonocompounds

Johnson, James C.; Attanasio, Ronald

doi:10.1159/000150000

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…Despite its shortcomings, the isobologram concept was intuitively attractive and in 1954, the isobologram was independently rediscovered by Gertrude Elion and coworkers (Elion et al, 1954) and has been used extensively for many years to evaluate drug interactions in many fields (Ahmed and Tyrell, 1986;Allen et al, 1982;Fraser-Smith et al, 1985;Huggins et al, 1984;Johnson and Attanasio, 1987;Spector et al, 1985;Streifel and Howell, 1981;Webb, 1963). Recently, increased interest in the isobologram concept has brought about significant improvements in isobologram methodology~ Isobolograms have been estimated from mathematical models (Carter et al, 1988) and analyzed statistically (Berenbaum, 1988;Gessner, 1988).…”

Section: Dose-response Surfaces and Isobologramsmentioning

confidence: 99%

A three-dimensional model to analyze drug-drug interactions

1990

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Nearly four generations of investigators have studied combined drug effects. Their methods of generating and analyzing data have changed dramatically over the years but the basic problem has not. This review examines the inherent difficulties in analyzing combined drug effects and evaluates modern methods of describing these interactions. Researchers have traditionally used two-dimensional (2-D) methods to approximate the actual three-dimensional (3-D) nature of drug interactions. We conclude that these 2-D methods are often inadequate when used to analyze synergistic and antagonistic drug interactions in antiviral and anticancer chemotherapy. We propose a direct and pragmatic 3-D approach to the problem, made possible by microcomputers and sophisticated graphics programs. This procedure directly elucidates the shape of the dose-response surface, identifies the regions of statistically significant synergy and antagonism, and quantitates these effects. It also greatly simplifies the problem since a 3-D surface presents complete drug interactions in a way that can be easily interpreted. We will show that understanding the shape of the resulting 3-D surface is essential to an understanding of complex drug interactions. This new method facilitates the rigorous analysis of drug-drug interactions and offers investigators powerful new tools to analyze combinations of antiviral and anticancer drugs.

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Section: Dose-response Surfaces and Isobologramsmentioning

confidence: 99%

A three-dimensional model to analyze drug-drug interactions

1990

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“…VR684) was propagated at 38° on chicken embryo fibroblasts (CEF) as previously described in media con sisting of equal parts of Dulbecco's modified Eagle's medium and Ham's F-12 (DMEM-F12) medium con taining 5% v/v fetal calf serum (FCS) [17]. Embryonated chicken eggs were obtained from pathogen-free flocks (Hyline International).…”

Section: Viruses and Cellsmentioning

confidence: 99%

“…DVE is caused by the Anatid herpesvirus (AHV), a term proposed and recommended by the Herpesvirus Study Group [9], Biological studies of the virus and its interactions with cells have been aided by the availability of neutralization antisera and a plaque assay ef fective, at least, for some of the AHV isolates [10][11][12], Although the physical description of the virus as obtained by electron microscopy [13,14], the biology of infection as obtained by single-step experiments [15], and initial charac terizations of the virus and viral nucleic acid by nuclease resistance [13,16] indicate that the viral genome is DN A, no reports other than a study of viral multiplication inhibition by phosphono compounds and acyclovir [17] have been pub lished which serve to confirm this finding.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of the DNA of Anatid Herpesvirus 1

1993

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A plaque-purified isolate of the Holland strain of Anatid herpesvirus (AHV-ppc3) was purified by differential and buoyant density sedimentation. The virus buoyant density was 1.215 g/cm³ in sucrose. AHV-ppc3 DNA was analyzed by sedimentation velocity studies in neutral or alkaline sucrose gradients. Based upon a comparison with T4 DNA, the DNA of AHV-ppc3 was found to have a sedimentation coefficient of 59.7 S and a molecular mass of 1.19 × 10⁸ daltons. Between 15 and 22 bands were observed in agarose gel electrophoresis with AHV DNA cut by BarnHl, EcoRl, Pstlor BgHIThe possibility of isometric forms is indicated by the finding of restriction fragments having molar ratios differing from 1.0. The mean molecular mass calculated from the fragments was 1.18 × 10⁸ daltons. Terminal fragments were identified using exonuclease II and BgHI. In alkaline sucrose gradients, AHV DNA fragments with the largest of the most abundant species have a sedimentation coefficient of 69 S and a calculated mass of 6.0 × 10⁷ daltons. The buoyant density of AHV-ppc3 DNA in cesium chloride was 1.723 g/cm³ corresponding to a % G + C content of 64.3. This finding was supported by thermal melts of the DNA in SSC/10 in which the thermal melting point was 82.7°. The data support a model for AHV in which the viral duplex DNA is linear, without covalently closed termini or significant base modifications, but with single strand nicks or gaps. The % G + C content of AHV DNA is the highest reported for any avian herpesvirus in the α-herpesvirinea subgroup.

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Section: A B Cmentioning

confidence: 99%

“…The resulting multiple dose-response curves were easily interpretable and were equivalent to taking vertical cross sections through the dose-response surface parallel to the axis of the first drug. This method of plotting is simple and is used often to make initial qualitative determinations of drug interactions (Bauer, 1954;Jackson, 1984;Johnson and Attanasio, 1987;MacKay, 1981). An example of data displayed in this manner is seen in Fig.…”

Section: Multiple Dose-response Curvesmentioning

confidence: 99%

A three-dimensional model to analyze drug-drug interactions

1991

Antiviral Research

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Nearly four generations of investigators have studied combined drug effects. Their methods of generating and analyzing data have changed dramatically over the years but the basic problem has not. This review examines the inherent difficulties in analyzing combined drug effects and evaluates modem methods of describing these interactions. Researchers have traditionally used two-dimensional (2-D) methods to approximate the actual three-dimensional (3-D) nature of drug interactions. We conclude that these 2-D methods are often inadequate when used to analyze synergistic and antagonistic drug interactions in antiviral and anticancer chemotherapy. We propose a direct and pragmatic 3-D approach to the problem, made possible by microcomputers and sophisticated graphics programs. This procedure directly elucidates the shape of the dose-response surface, identifies the regions of statistically significant synergy and antagonism, and quantitates these effects. It also greatly simplifies the problem since a 3-D surface presents complete drug interactions in a way that can be easily interpreted. We will show that understanding the shape of the resulting 3-D surface is essential to an understanding of complex drug interactions. This new method facilitates the rigorous analysis of drug-drug interactions and offers investigators powerful new tools to analyze combinations of antiviral and anticancer drugs.

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Synergistic Inhibition of Anatid Herpesvirus Replication by Acyclovir and Phosphonocompounds

Cited by 9 publications

References 17 publications

A three-dimensional model to analyze drug-drug interactions

A three-dimensional model to analyze drug-drug interactions

Molecular Characterization of the DNA of Anatid Herpesvirus 1

A three-dimensional model to analyze drug-drug interactions

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