Table 1.
Selected EV-A71 antivirals with translational potential.
| Inhibitor | Remark | Inhibited | Not inhibited | Ref. |
|---|---|---|---|---|
| Capsid inhibitors | ||||
| Pleconaril | Activity against EV-A71 is controversial Dropped out of clinical trial for rhinovirus infection |
EV-D68, RV-87, RV-A, RV-B | PV-1, RV-B17, RV-A45, RV-C | 56,58,59,64 |
| Vapendavir | Dropped out of clinical trial for rhinovirus infection | EV-A71. EV-C, RV-A, RV-B | EV-D68 | 55,57,65 |
| Pirodavir | Dropped out of clinical trial for rhinovirus infection | EV-A71, EV-D68, EV-A, EV-B, EV-C, EV-D, RV-A, RV-B | RV-A8, RV-A25, RV-A45, RV-87, RV-C | 57,64, 65, 66 |
| PR66 | In vivo antiviral efficacy against EV-A71 in mice | EV-A71 | EV-D68, CV-A16, CV-B1, CV-B2, CV-B3, Echovirus 9, rhinovirus | 60 |
| NLD-22 | Favorable PK properties In vivo antiviral efficacy against EV-A71 in mice |
EV-A71 | – | 61 |
| VP1-14 | Favorable PK properties In vivo antiviral efficacy against EV-A71 in mice |
EV-A71 | – | 62 |
| ICA135 | In vivo antiviral efficacy against CV-A10 in mice | CV-A10, EV-A71, CV-A16, CV-B3, PV-1, EV-D68 | – | 63 |
| CB-30 | Binds to the five-fold axis of the EV-A71 capsid | EV-A71, HIV-1, HIV-2 | – | 67 |
| Suramin | Polypharmacology In vivo antiviral efficacy against EV-A71 in mice and rhesus monkeys |
EV-A71, CV-A2, CV-A3, CV-A10, CV-A12, CV-A16, CV-A9, ECHO25 | ECHO20, PV1-3, EV-D68 | 68, 69, 70, 71 |
| Brilliant black BN (E151) | Binds to the five-fold axis of the EV-A71 capsid In vivo antiviral efficacy against EV-A71 in mice |
EV-A71, CV-A16, CV-A6 | CV-A4, CV-A10 | 72 |
| 2C inhibitor | ||||
| (S)-Fluoxetine | Lack of efficacy against EV-D68 in clinical trials (S)-enantiomer is more active | CV-B3, EV-D68, HRV-A2, HRV-B14 | EV-A71, PV-1 | 73, 74, 75 |
| 2C-12b | Analog of fluoxetine | EV-A71, EV-D68, CV-B3, PV-1, CV-A24, HRV-A2, HRV-B14 | – | 76 |
| Dibucaine | Identified through drug repurposing | EV-A71, EV-D68, CV-B3 | PV-11, RV-A2, RV-B14 | 77 |
| 2C-12a | Dibucaine analog; Did not inhibit Na+ channel |
EV-D68 | – | 78 |
| JX040 | Derived from a HTS hit | CV-B3, EV-A71, PV-1 | – | 79 |
| 2C-7d | Derived from a HTS hit | EV-A71, EV-D68, CV-B3 | – | 80 |
| 3A protein inhibitor | ||||
| Enviroxime | Failed in phase II trial for rhinovirus infection; PI4KIIIβ was also suggested as the drug target |
PV1-3, RV14, RV16, CA21, CB3, RV-87, EV-A71, EV-D68 | – | 64,65,81, 82, 83 |
| Itraconazole | Mutations in 3A confer drug resistance; OSBP was also suggested as the drug target |
EV-A71, CV-A16, CV-B3, PV-1, HRV14, EV-D68 | Equine rhinitis A virus | 84,85 |
| 3Cpro inhibitor | ||||
| Rupintrivir | Failed in phase II trial for rhinovirus infection | EV-A71, CV-A16, EV-D68, RV-87, norovirus, human rhinoviruses | SARS-CoV-2 | 64,65,86, 87, 88, 89 |
| GC-376 | Veterinary drug candidate for FIPV infection in cats | EV-A71, EV-D68, HRV18, HRV51, HRV68 | – | 88 |
| 3Dpol inhibitor | ||||
| Gemcitabine | Identified through drug repurposing; Synergistic effect with interferon-β |
EV-A71, EV-D68, CV-B3, CV-A6, CV-A16, E-7, PV-1, DENV, CHIKV | – | 90 |
| Sofosbuvir | In vivo antiviral efficacy against EV-A71 in mice | EV-A71 | – | 90 |
| FNC | HIV clinical candidate | EV-A71, CV-A16, CV-A6, EV-D68, CV-B3 | – | 91 |
| Favipiravir (T-705) | Synergistic effect with suramin | EV-A71, EV-D68 (not all subtypes) | – | 65,92 |
| NITD008 | Failed in clinical trial for flavivirus infection | EV-A71 | – | 93 |
| IRES inhibitor | ||||
| DMA-135 | Binds to the IRES stem loop 2 | EV-A71 | – | 94 |
| Prunin | Mutations in IRES confer drug resistance; In vivo antiviral efficacy against EV-A71 infection in mice |
EV-A71 | – | 95 |
| Emetine | In vivo antiviral efficacy against EV-A71 infection in mice | EV-A71, CV-A16, CV-B1, EV-D68, Echovirus 6 | – | 96 |
| Host-targeting antivirals | ||||
| OSW-1 | Decreases OSBP level | EV-A71, CV-B3, CV-A21, RV-B14 | – | 97 |
| MDL-860 | Allosteric inhibitor of PI4KB | RV-1, RV-2, RV-8, RV-64, PV-2, EV-A71, EV-D68 | – | 98,99 |
| RYL-634 | DHODH inhibitor | HCV, DENV, ZIKV, CHIV, EV-A71, HIV, RSV | – | 100 |
–Not available.