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Antiviral agents against HAV | Types | Description | Ref. |
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HATs |
Interferons | (i) Interferon-alpha (IFN-α) | (i) IFN-α has antiviral activity against HAV replication | [117–121] |
(ii) Interferon-gamma (IFN-γ) | (ii) Its use is unsafe for severe HAV infections, including fulminant hepatitis |
(iii) Interferon-lambda (IL-29, IL-28A and B) | (iii) Recombinant IFN-γ displays antiviral activity against chronic HAV infection |
(iv) IL-29 and IL-28A inhibit HAV IRES-mediated translation |
(v) Compared to IFN-α, it had fewer side effects, such as hematological cytotoxicities or depression |
Ribavirin | | (i) Acts against RNA and DNA viruses | [122, 123] |
(ii) Moderately affects HAV replication in cell culture |
Amantadine | | (i) Inhibits viral antigen synthesis, HAV IRES-mediated translation, and HAV replication | [117, 124] |
(ii) Its effects may be strain-dependent |
(iii) Stronger inhibitory effects on HAV replication were seen when amantadine was combined with IFN-α or IL-29 |
Agents against host enzymes and cellular factors | (i) Autoantigen la | (i) These proteins may interact with HAV IRES RNA and might be associated with HAV replication and IRES-mediated translation | [62, 125–128] |
(ii) GAPDH |
(iii) Polypyrimidine tract-binding protein |
(iv) Poly(C) binding protein 2 |
(v) Polyadenylate-bindingprotein-1 (PABP) |
(vi) Eukaryotic translation initiation factor 4E (eIF4E) an4G (eIF4G) |
(vii) Janus kinase (JAK) inhibitor |
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DAAs |
Cysteine protease inhibitors | (i) Peptide aldehyde | (i) Play a crucial part in the HAV polyprotein’s processing, thus affecting HAV replication | [129–132] |
(ii) A peptidyl monofluoromethyl ketone (peptidyl-FMK) |
(iii) Beta-lactones |
(iv) Hexanucleotide (G(5)T) |
siRNAs | (i) siRNAs against the HAV 2C- and 3D-coding regions | (i) siRNAs generally knock down target genes and prevent them from producing a functional protein | [133–136] |
(ii) This group of siRNAs acts against HAV nonstructural protein-coding regions related to HAV replicon replication |
(ii) RNase III endoribonuclease-prepared siRNAs (esiRNAs) and some short hairpin RNAs (shRNAs) | (iii) They target HAV IRES and suppress HAV IRES-mediated translation |
(iv) Compared to a single transfection, subsequent siRNA transfections targeting different HAV genome sequences may have a more effective and long-lasting silencing effect |
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