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Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies
Antiviral Research ( IF 7.6 ) Pub Date : 2017-07-01 , DOI: 10.1016/j.antiviral.2017.06.022
Donald F. Smee , Mark N. Prichard

Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antagonistic), or neutral (no or minimal interaction). Interactions of two known inhibitors of vaccinia virus replication, cidofovir and 6-azauridine, used in combination by PR assay yielded a VS value of 265, indicative of strong synergy. By VYR, the VS value was only 37, or weak synergy using the same criterion, even though profound log10 reductions in virus titer occurred at multiple drug combinations. These results confirm that the differences in VS values is dependent of the measurement scale, and not that the degree of synergy differed between the assays. We propose that for logarithmic data, the calculated VS values will be lower for significant synergy and antagonism and that volumes of >10 μM2log10 PFU/ml (or other units such as μM2log10 genomic equivalents/ml or μM2log10 copies/ml) and <-10 μM2log10 PFU/ml are likely to be indicative of strong synergy and strong antagonism, respectively. Data presented here show that the interaction of cidofovir and 6-azauridine was strongly synergistic in vitro.



中文翻译:

抗病毒研究中百分比和对数数据的三维协同分析的比较

使用三维MacSynergy II软件进行了细胞培养抗病毒实验,以了解噬菌斑减少(PR)产生的百分比数据与病毒产量减少(VYR)分析得出的对数数据之间的关系。百分比和对数数据之间的关系以前尚未研究过。药物相互作用的解释基于协同作用量(VS)的计算,可以是正的(协同作用),负的(拮抗作用)或中性的(无相互作用或最小相互作用)。通过PR测定法结合使用的两种已知的痘苗病毒复制抑制剂西多福韦和6-氮杂尿嘧啶的相互作用产生的VS值为265,表明具有强大的协同作用。通过VYR,VS值仅为37,或使用相同标准的弱协同作用,即使对数很深在多种药物组合中,病毒滴度降低了10。这些结果证实,VS值的差异取决于测量范围,并且各试验之间的协同程度没有差异。我们建议,对于对数数据,所计算的VS值将是显著协同作用和拮抗作用和该卷下> 10μM 2日志10  PFU / ml的(或其它单元,例如μM 2日志10基因组当量/ ml或μM 2日志10个拷贝/ ml)和<-10μM 2日志10 PFU / ml可能分别指示强烈的协同作用和强烈的拮抗作用。此处提供的数据表明,西多福韦与6-氮杂尿苷的相互作用在体外具有强烈的协同作用。

更新日期:2017-07-01
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