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Volume 14, Number 4—April 2008

Synopsis

Potential Use of Antiviral Agents in Polio Eradication

Armando M. De Palma*, Gerhard Pürstinger†, Eva Wimmer†, Amy K. Patick‡, Koen Andries§, Bart Rombaut¶, Erik De Clercq*, and Johan Neyts*Comments to Author 
Author affiliations: *University of Leuven, Leuven, Belgium; †University of Innsbruck, Innsbruck, Austria; ‡Pfizer Global Research and Development, San Diego, California, USA; §J&J Pharmaceutical Research and Development, Beerse, Belgium; ¶Vrije Universiteit Brussel, Brussels, Belgium;

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Table

Inhibitory activity of selected compounds against replication of poliovirus Sabin strains 1, 2, and 3 in HeLa cells, as determined by a CPE reduction assay*

Compound EC50 (µmol/L)
Toxicity (CC50;µmol/L) TI (min–max)
PV1 PV2 PV3
Capsid binders
Pirodavir analog (R78206) 0.76 ± 0.18 0.22 ± 0.19 0.11 ± 0.10 27 ± 34 35–245
Pleconaril >100 1.1 ± 0.6 0.22 ± 0.15 66 ± 6 <0.66–300
Pirodavir (R77975)
10 ± 1
1.7 ± 0.1
0.56 ± 0.03
>100
>10–>179
Protease inhibitors
Rupintrivir 0.022 ± 0.028 0.041 ± 0.024 0.0052 ± 0.0046 >100 >2,439–>19,231
Compound 1
0.26 ± 0.24
0.31 ± 0 .21
0.060 ± 0 .000
>100
>322–>1,667
3A inhibitor
Enviroxime
0.2 ± 0.25
0.056 ± 0.020
0.035 ± 0.029
58 ± 6
290–1,657
Nucleoside analogs
Ribavirin 57 ± 13 64 ± 4 55 ± 7 >100 >1.6–>1.8
2'-C-methylcytidine† 15 ± 18 29 ± 27 3.9 ± 2.3 >100 >3.4–>26
2'-C-methyladenosine 5.5 ± 0.0 5.6 ± 0.1 5.4 ± 0.4 84 ± 0 15
4’-azidocytidine
>100
>100
>100
>100
><1
2C inhibitors
HBB 300 ± 68 225 ± 128 295 ± 88 >400 >1.3–>1.8
MRL-1237
5.3 ± 0.3
4.6 ± 1.4
3.8 ± 2.5
>100
>19–>26
Unknown target
MDL-860 6.0 ± 1.6 3.6 ± 2.2 2.2 ± 1.5 >100 >17–>45

*CPE, cytopathic effect; EC50, 50% effective concentration; CC50, 50% cytotoxic concentration; PV, poliovirus; TI, therapeutic index (CC50/EC50); min, minimum; max, maximum; HBB, 2-(α-hydroxybenzyl)-benzimidazole.
†Valopicitabine (oral valine ester prodrug of 2′-C-methylcytidine).

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