Figure 5: Evaluation of the synergism of suramin (7) in combination with competitive in vitro inhibitors of HN.
From: A dual drug regimen synergistically blocks human parainfluenza virus infection
Data sets in red and blue correspond to suramin (7)—compound 5 or suramin (7)—zanamivir (3) combinations, respectively. (a) Dose-response curves of each individual compound. Suramin (7) was evaluated twice, for each of the combinations with suramin and compound 5. The antiviral effect was determined by measurement of foci size. (b) Median-effect representation of the dose-response curves for each individual compound, using Equation (4). m is the linear regression slope, fa is the “fraction affected”, or (% effect) ÷100. (c) Normalised isobologram that represents, for each combination, the normalised dose of each compound individually required to reach the observed effect in combination (Equation (3)). D1 is the dose of a compound 1 in combination required to achieve x% of inhibition, while Dx1 is the dose of a compound alone required to achieve x% of inhibition. Data points in zone a, b and c correspond to combinations with synergistic, additive or antagonistic effects, respectively. (d) CI-effect plot representing the combination index CI, calculated using Equation (2), of each combination as a function of their associated antiviral effect. The zones a, b and c are the same as the ones described in (c). (e) log(DRI)-effect plot representing the drug reduction index (DRI) of compounds as a function of their antiviral effect in combination. The DRI is calculated for each drug in each combination according to Equation (5), and represents the dilution factor required for a drug to reach the same level of inhibition individually compared with it when in combination. All combinations were tested in quadruplicate, post-adsorption, by a focus reduction assay. The results are representative of 3 independent experiments.
