Antiviral Agents in Development for Zika Virus Infections
Abstract
:1. Introduction
2. Genome and Replicative Cycle
3. Potential Therapeutic Options for the Treatment of ZIKV Infection
3.1. Direct-Acting Antivirals
3.2. Host-Targeting Antivirals
4. Who Benefits from ZIKV Therapies?
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name | Amino Acid Residues | Function |
---|---|---|
C | 122 | Generation of nucleocapsid (encapsulates genomic RNA) |
prM | 168 | Protects E protein during assembly |
E | 500 | Envelope glycoprotein (membrane binding and fusion) |
NS1 | 352 | Replication and immune response regulation |
NS2A | 226 | Replication and capsid assembly |
NS2B | 130 | NS3 cofactor |
NS3 | 617 | Serine protease NTPase, RNA helicase |
NS4A | 127 | Viral membrane formation |
2K | 23 | Signal peptide |
NS4B | 251 | Inhibits antiviral state |
NS5 | 903 | RNA dependent RNA polymerase |
Direct-Acting Antivirals | |||
Name | Mode of action | In vitro | In vivo |
7-deaza-2-CMA | RdRp inhibitor | √ | √ |
2-CMA, 2-CMC, 2-CMG, 2-CMU | RdRp inhibitor | √ | X |
Favipiravir | RdRp inhibitor | √ | X |
NITD008 | Pyrimidine synthesis inhibitor | √ | √ |
Sofosbuvir | RdRp inhibitor | √ | √ |
BCX4430 * | RdRp inhibitor | √ | √ |
Sinefungin | Pan-methyltransferase inhibitor | √ | X |
Myricetin, quercetin, luteolin, isorhamnetin, apigenin, curcumin | NS2B-NS3 protease inhibitor | √ | X |
Niclosamide, and nitazoxanide | NS2B-NS3 protease inhibitor | √ | X |
Temoporfin | NS2B-NS3 protease inhibitor | √ | √ |
Novobiocin | NS2B-NS3 protease inhibitor | √ | √ |
Suramin | NS3 inhibitor | √ | X |
Host-Targeting Antivirals | |||
Name | Mode of action | In vitro | In vivo |
Ribavirin | Several mechanisms including purine synthesis inhibitor | √ | √ |
Merimepodib and mycophenolic acid | Inosine monophosphate dehydrogenase (IMPDH) inhibitors | √ | X |
Azathioprine | Purine synthesis inhibitor | √ | X |
6-azauridine, 5-fluorouracil | Pirimidine synthesis inhibitor | √ | X |
lovastatin | HMG-CoA reductase inhibitor | √ | X |
Azithromycin | Unknown mechanisms of action against ZIKV | √ | X |
Chloroquine | Inhibition of pH-dependent steps of viral replication | √ | X |
Saliphenylhalamide | Viral entry inhibitor | √ | X |
Obatoclax mesylate (GX15-070) | Bcl-2 protein inhibitor | √ | X |
PHA-690509 | Cyclin-dependent kinase inhibitor | √ | X |
MK-801, agmatine, and ifenprodil | Neuronal cell death inhibitor | √ | X |
Memantine | Neuronal cell death inhibitor | √ | √ |
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Baz, M.; Boivin, G. Antiviral Agents in Development for Zika Virus Infections. Pharmaceuticals 2019, 12, 101. https://doi.org/10.3390/ph12030101
Baz M, Boivin G. Antiviral Agents in Development for Zika Virus Infections. Pharmaceuticals. 2019; 12(3):101. https://doi.org/10.3390/ph12030101
Chicago/Turabian StyleBaz, Mariana, and Guy Boivin. 2019. "Antiviral Agents in Development for Zika Virus Infections" Pharmaceuticals 12, no. 3: 101. https://doi.org/10.3390/ph12030101