Table 7.
(A) Synergistic effect of several inhibitors, measured by MacSynergy II synergistic effect [µM2%] *. (B) Synergistic effect of several inhibitors, measured by SynergyFinder ZIP score *. (C) Synergistic effect of gemcitabine with several concentration of ribavirin, measured by CompuSyn combination index.
| (A) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Synergistic Effect [µM2;%] ‡ | Virus | Pocapavir (V-073) |
Vapendavir (BTA798) |
Pleconaril | Disoxaril | Arildone | Enviroxime | HBB | MDL-860 | NITD008 | GPP3 | Itraconazole | Favipiravir | Suramin | Ref. | |
|
AG-7404/
V-7404 |
PV Sabin 1 | 580 | 463 | / | / | / | / | / | / | / | / | / | / | / | [115] | |
| PV Sabin 2 | 459 | 245 | / | / | / | / | / | / | / | / | / | / | / | |||
| PV Sabin 3 | 288 | 579 | / | / | / | / | / | / | / | / | / | / | / | |||
| MDL-860 | CVB1 Connecticut | / | / | 22.5 | / | / | / | / | / | / | / | / | / | / | [111,112] | |
| CVB3 Woodruff | / | / | 61.1 | / | / | / | / | / | / | / | / | / | / | |||
| Guanidine.HCl | CVB1 Connecticut | / | / | 58.4 | / | / | / | / | 47.5 | / | / | / | / | / | ||
| CVB3 Nancy | / | / | / | / | / | / | / | 1.1 | / | / | / | / | / | |||
| CVB3 Woodruff | / | / | 56.2 | / | / | / | / | 83.9 | / | / | / | / | / | |||
| Oxoglaucine | CVB1 Connecticut | / | / | 27.0 | / | / | / | / | 7.8 | / | / | / | / | / | ||
| CVB3 Nancy | / | / | / | / | / | / | / | 220.6 | / | / | / | / | / | |||
| CVB3 Woodruff | / | / | 18.6 | / | / | / | / | 151.0 | / | / | / | / | / | |||
| Enviroxime | CVB1 Connecticut | / | / | / | 82 | −39 a | / | 253 | / | / | / | / | / | / | ||
| PTU-23 | CVB1 Connecticut | / | / | / | 314 | 519 | 373 | 275 | / | / | / | / | / | / | ||
| HBB | CVB1 Connecticut | / | / | / | 689 | 852 | 253 | / | / | / | / | / | / | / | ||
| S-7 | CVB1 Connecticut | / | / | / | / | / | 399 | 368 | / | / | / | / | / | / | ||
| Compound 1 | CVB4 Edwards | / | / | 147 | / | / | / | / | / | / | / | / | / | / | [109] | |
| YZ-LY-0 | 0.125 µM | EV-A71 SK-EV006 |
/ | / | / | / | / | / | / | / | −400–−300 | 0–100 | / | / | / | [118] |
| 1 µM | / | / | / | / | / | / | / | / | −100–0 | 0–100 | / | / | / | |||
| Rupintrivir | EV-A71 FY573 | / | / | / | / | / | / | / | / | / | / | 450.64 | 438.07 | 4.96 | [116] | |
| Favipiravir | EV-A71 FY573 | / | / | / | / | / | / | / | / | / | / | −88.11 | / | 337.59 | ||
| Suramin | EV-A71 FY573 | / | / | / | / | / | / | / | / | / | / | −246.23 | 337.59 | / | ||
| GW5074 | EV-A71 FY573 | / | / | / | / | / | / | / | / | / | / | −167.68 | / | / | ||
| (B) | ||||||||||||||||
| ZIP Synergy Score [−30/30] † | Virus | Pleconaril | Rupintrivir | Ref. | ||||||||||||
| Rupintrivir | E1 Farouk (A549 cells) | 18.0 | / | [110] | ||||||||||||
| E1 Farouk (RPE cells) | 18.9 | / | ||||||||||||||
| Vemurafenib | E1 Farouk (A549 cells) | 13.6 | 15.6/16.00 | |||||||||||||
| E1 Farouk (RPE cells) | 20.2 | 17.2 | ||||||||||||||
| Pleconaril | E1 Farouk (A549 cells) | 18.0/18.3 | 18.0/18.3 | |||||||||||||
| E1 Farouk (RPE cells) | 18.9 | 18.9 | ||||||||||||||
| Cycloheximide | E1 Farouk (A549 cells) | / | 10.7 | |||||||||||||
| Remdesivir | E1 Farouk (A549 cells) | / | 8.23 | |||||||||||||
| Dalbavancin | E1 Farouk (A549 cells) | / | 8 | |||||||||||||
| Anisomycin | E1 Farouk (A549 cells) | / | 6.39 | |||||||||||||
| Emetine | E1 Farouk (A549 cells) | / | 4.1 | |||||||||||||
| Digoxin | E1 Farouk (A549 cells) | / | −5.6 | |||||||||||||
| Homoharringtonine | E1 Farouk (A549 cells) | / | −5.7 | |||||||||||||
| Halofuginone | E1 Farouk (A549 cells) | / | −7.5 | |||||||||||||
| Obatoclax | E1 Farouk (A549 cells) | / | −7.8 | |||||||||||||
| Gemcitabine | E1 Farouk (A549 cells) | / | −8.7 | |||||||||||||
| (C) | ||||||||||||||||
| Concentration of Ribavirin (µM) | 25 | 50 | 100 | 200 | 400 | Ref. | ||||||||||
|
Combination Index with 0.4 µM of gemcitabine °
(CVB3 on Vero cells) |
0.28 | 0.23 | 0.15 | 0.14 | 0.14 | [120] | ||||||||||
(A) * Compounds evaluated in clinical assays have their rows and columns shaded. ‡ Synergistic effect (SE) is calculated using the MacSynergy II software. It measures strong synergistic effect (if SE > 100 µM2%), synergistic effect (if 50 µM2% < SE < 100 µM2%), additive effect (if 0 < SE < 50 µM2%) and antagonistic effect (if SE < 0 µM2%). a Combination of enviroxime and arildone led to an antagonism effect measured at −39 µM2%. (B) * Compounds evaluated in clinical assays have their rows and columns shaded. † ZIP Score is calculated using SynergyFinder version 3 software. It measures strong synergistic effect (if ZIP Score > 15), synergistic effect (if 5 < ZIP Score < 15), additive effect (if −5 < ZIP Score < 5) and antagonistic effect (if ZIP Score < −5). (C) ° Combination Index (CI) is calculated using CompuSyn software (https://compusyn.software.informer.com/, accessed on 30 June 2024). It measures synergistic effect if it’s inferior to 1 (CI < I), additive effect if equal to 1 (CI = 1), antagonist effect if superior to 1 (CI > 1).