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Table 1 List of antivirals against EV-71 infection tested in vitro and in vivo

From: Recent developments in antiviral agents against enterovirus 71 infection

Antivirals

EV-71 genotype tested

IC50/EC50

In vitro cell type

Resistant mutants

In vivo mouse model

Reference

Therapeutics targeting viral attachment and entry

      

Molecular decoys

      

Recombinant SCARB2

B3

N/R

RD

  

[28]

PSGL-1

C2

N/R

L-PSGL-1.1

  

[29]

Heparin mimetics

      

  Heparin

C2

205 μg/ml

Vero, RD

  

[25, 36]

  Heparan sulfate

C2

290 μg/ml

Vero

  

[36]

  Pentosan polysulfate

C2

238 μg/ml

Vero

  

[36]

  Dextran sulfate

B4

N/R

RD

  

[25]

Suramin/NF449

B1, B3, B4

6.7 μM

RD

VP1 E98Q, K244R

 

[25, 37]

Kappa carrageenan

B4

N/R

Vero

  

[38]

Enviroxime-like compounds

      

  AN-12-H5

B1

0.55 μM

RD

VP1 M119L, VP3 R227K

 

[124]

  AN-23-F6

B1

0.15 μM

RD

VP1 A224T

 

[124]

Receptor antagonists

      

Anti-SCARB2 antibodies

B3

N/R

RD

  

[28]

Anti-PSGL-1 antibodies

B3, B4, C1, C2, C4

N/R

Jurkat

  

[29]

Bovine lactoferrin

C2, MP4a

10.5 – 24.5 μg/ml

RD, Vero, SK-N-SH

 

17-days old ICR

[42, 43]

Human lactoferrin

N/R

103.3 – 185.0 μg/ml

RD, Vero

  

[42]

SP40 peptide

A, B4, C2

6 – 9.3 μM

RD, HeLa, HT-29, Vero

  

[39]

Anti-heparan sulfate peptide

B4

N/R

RD

  

[25, 40]

Therapeutics targeting viral uncoating

      

Pyridyl imidazolidinone

      

  BPROZ-299

C2

0.02 μM

RD

VP1 V192M

 

[52]

  BPROZ-284

A, B1, C2

0.04 μM

RD

  

[49]

  BPROZ-194

C2

1.552 μM

RD

VP1 V192M

 

[51, 52]

  BPROZ-160

C2

0.011 μM

RD

VP1 V192M

 

[52]

  BPROZ-112

A, B1, C2

0.04 μM

RD

  

[49]

  BPROZ-103

C2

0.13 μM

RD

VP1 V192M

 

[52]

  BPROZ-101

A, B1, C2

0.0012 μM

RD

  

[52, 53]

  BPROZ-074

A, B1, C2

0.0008 – 0.018 μM

RD

VP1 V192M

 

[52, 54]

  BPROZ-033

A, B1, C2

0.0088 – 0.069 μM

RD

  

[52, 54]

WIN51711

B3

N/R

RD

  

[48]

Pleconaril

A

0.13-0.54 μg/ml

RD

 

1-day old ICR

[56]

BW683C

A

> 10 μM

HEp-2

  

[59]

Compound 3 g

A

0.45 μM

HEp-2

  

[59]

BTA39

A

0.001 μM

Vero

  

[57]

BTA188

A

0.082 μM

Vero

  

[57]

Therapeutics targeting viral translation

      

RNA-based therapeutics

      

  siRNA

B4

< 1 nM

RD

 

1-day old Balb/c

[67–72]

  shRNA

B4

< 1 nM

RD

 

1-day old Balb/c

[67–72]

Quinacrine

C4

9.71 μM

RD

  

[75]

Amantadine

Pseudo-EV-71

N/R

COS-1

  

[78]

Therapeutics targeting viral polyprotein processing

      

2A inhibitor

      

  LVLQTM peptide

C4

9.6 μM

HeLa

  

[83]

3C inhibitors

      

  Rupintrivir

C4

0.014 μM

RD

 

2-days old ICR

[93]

  Compound 10b

C2

0.018 μM

RD

  

[96]

  Fisetin

CMUH01*

85 μM

RD

  

[97]

  Rutin

CMUH01*

110 μM

RD

  

[97]

Therapeutics targeting viral replication

      

2B inhibitor

      

  DIDS

C4

N/R

RD

  

[109]

2C inhibitors

      

  Metrifudil

B1

1.3 μM

RD

2C E325G

 

[37]

  N6 benzyladenosine

B1

0.1 μM

RD

2C H118Y, I324M

 

[37]

  Guanidine-HCl

B3

N/R

RD

2C M193L

 

[119]

3A inhibitors

      

  Enviroxime

A

0.15 μM

Vero

  

[112]

  AN-12-H5

B1

0.55 μM

RD

3A E39G

 

[124]

  AN-23-F6

B1

0.15 μM

RD

  

[124]

  TTP-8307

A

> 60 μM

Vero

  

[112]

  GW5074

B1

6.4 μM

RD

  

[124]

3D inhibitors

      

  DTriP-22

A, B2, C2

0.3 μM

RD

3D R163K

 

[130]

Ribavirin

C2, M2b

266 μM

RD, SK-N-SH, N18

3D G64R, S264L

12-days old ICR

[129]

Heat-shock protein 90 inhibitor

      

  Geldanamycin

B4, C2

N/R

RD

  

[105]

  17-AAG

C2, C4

N/R

N/R

 

7-days old hSCARB-Tg C57BL/6 mice

[105]

  1. aMouse-adapted EV-71 strain Tainan/4643/98 (C2); bMouse-adapted EV-71 strain derived from MP4 with additional two passages in mice; *EV-71 strain with unidentified genotype; and N/R means not reported.
  2. RD: rhabdomyosarcoma cells; Vero: African green monkey kidney cells; SK-N-SH: human neuroblastoma cells; N18: mouse neuroblastoma cells; HeLa: human cervical adenocarcinoma epithelial cells; HT-29: human colon adenocarcinoma cells; HEp-2: HeLa contaminant cells; Jurkat: human T lymphocytes cells; and COS-1: monkey kidney fibroblast cells.