Enterovirus 68 future or investigational therapies: Difference between revisions
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==Overview== | ==Overview== | ||
Currently, there are no specific therapies targeting EV-D68. Although the management of enteroviruses in general is only supportive, the development of pharmacologic therapies has recently emerged. [[Immune globulin]] therapy has demonstrated clinical and laboratory benefit among some patients with enterovirus infection. Antiviral medications against enteroviruses, such as [[pleconaril]], are currently being studied for patients with severe infections caused by other subtypes of enteroviruses. | |||
==Future or Investigational Therapies== | ==Future or Investigational Therapies== | ||
===Immune globulin=== | ===Immune globulin=== | ||
* Studies in neonates with enterovirus infection suggest a possible benefit of the | *Studies in neonates with enterovirus infection suggest a possible benefit of the administration of [[immune globulin]]<ref>{{Cite journal | ||
| author = [[Marc Tebruegge]] & [[Nigel Curtis]] | | author = [[Marc Tebruegge]] & [[Nigel Curtis]] | ||
| title = Enterovirus infections in neonates | | title = Enterovirus infections in neonates | ||
| Line 30: | Line 30: | ||
| pmid = 7620000 | | pmid = 7620000 | ||
}}</ref>, however, more studies need to be done do confirm the benefit of this treatment. | }}</ref>, however, more studies need to be done do confirm the benefit of this treatment. | ||
*The development of | *The development of IVIg with high levels of enterovirus antibody has shown benefit in ''in vitro'' and mouse models studies for enterovirus subtype 71. However, this has not been studied for EV-D68.<ref>{{Cite journal | ||
| author = [[Rui-Yuan Cao]], [[Jian-Feng Han]], [[Tao Jiang]], [[Xue Tian]], [[Man Yu]], [[Yong-Qiang Deng]], [[E.-De Qin]] & [[Cheng-Feng Qin]] | | author = [[Rui-Yuan Cao]], [[Jian-Feng Han]], [[Tao Jiang]], [[Xue Tian]], [[Man Yu]], [[Yong-Qiang Deng]], [[E.-De Qin]] & [[Cheng-Feng Qin]] | ||
| title = In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors | | title = In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors | ||
| Line 44: | Line 44: | ||
===Antiviral Medication=== | ===Antiviral Medication=== | ||
* Pleconaril has shown benefit | *There are no antiviral medications that specifically target EV-D68 only. Instead, antiviral medications against enteroviruses in general are also believed to be able to successfully target EV-D68. | ||
* The table shown below describes the possible targets for antiviral treatment against enterovirus infections.<ref name="ThibautLeyssen2011">{{cite journal|last1=Thibaut|first1=Hendrik Jan|last2=Leyssen|first2=Pieter|last3=Puerstinger|first3=Gerhard|last4=Muigg|first4=Alexandra|last5=Neyts|first5=Johan|last6=De Palma|first6=Armando Mirko|title=Towards the design of combination therapy for the treatment of enterovirus infections|journal=Antiviral Research|volume=90|issue=3|year=2011|pages=213–217|issn=01663542|doi=10.1016/j.antiviral.2011.03.187}}</ref><ref>{{Cite journal | *[[Pleconaril]] has shown benefit among patients with severe life-threatening enterovirus infections. This [[antiviral]] drug prevents the attachment of the [[virus]] to the host cell and integration of its [[RNA]] to the host [[DNA]].<ref name="RotbartWebster2001">{{cite journal|last1=Rotbart|first1=H. A.|last2=Webster|first2=A. D.|title=Treatment of Potentially Life-Threatening Enterovirus Infections with Pleconaril|journal=Clinical Infectious Diseases|volume=32|issue=2|year=2001|pages=228–235|issn=1058-4838|doi=10.1086/318452}}</ref> | ||
*The table shown below describes the possible targets for [[antiviral]] treatment against enterovirus infections.<ref name="ThibautLeyssen2011">{{cite journal|last1=Thibaut|first1=Hendrik Jan|last2=Leyssen|first2=Pieter|last3=Puerstinger|first3=Gerhard|last4=Muigg|first4=Alexandra|last5=Neyts|first5=Johan|last6=De Palma|first6=Armando Mirko|title=Towards the design of combination therapy for the treatment of enterovirus infections|journal=Antiviral Research|volume=90|issue=3|year=2011|pages=213–217|issn=01663542|doi=10.1016/j.antiviral.2011.03.187}}</ref><ref>{{Cite journal | |||
| author = [[Hendrik Jan Thibaut]], [[Armando M. De Palma]] & [[Johan Neyts]] | | author = [[Hendrik Jan Thibaut]], [[Armando M. De Palma]] & [[Johan Neyts]] | ||
| title = Combating enterovirus replication: state-of-the-art on antiviral research | | title = Combating enterovirus replication: state-of-the-art on antiviral research | ||
| Line 70: | Line 71: | ||
| style="padding: 5px 5px; background: #F5F5F5;" |Pleconaril, Pirodavirb, pyridazinyl oxime ethersb (BTA-39c), pyridyl imidazolidinonesc; NF-449c, V-073 | | style="padding: 5px 5px; background: #F5F5F5;" |Pleconaril, Pirodavirb, pyridazinyl oxime ethersb (BTA-39c), pyridyl imidazolidinonesc; NF-449c, V-073 | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |RNA replication | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |RNA replication (2C and 3B protein) | ||
| style="padding: 5px 5px; background: #F5F5F5;" |Enviroxime, TTP-8307, vinylacetylene analogs, GW5074c, Benzimidazoles, N(6)-benzyladenosine, metrifudil | | style="padding: 5px 5px; background: #F5F5F5;" |Enviroxime, TTP-8307, vinylacetylene analogs, GW5074c, Benzimidazoles, N(6)-benzyladenosine, metrifudil | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |RNA polymerase | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |RNA-dependent RNA polymerase | ||
| style="padding: 5px 5px; background: #F5F5F5;" |2′C–Me-cytidine, 4′-azidocytidine, 2′C-ME-adenosine, ribavirin, DTriP-22c, aurintricarboxylic acid, gliotoxin, amiloride | | style="padding: 5px 5px; background: #F5F5F5;" |2′C–Me-cytidine, 4′-azidocytidine, 2′C-ME-adenosine, ribavirin, DTriP-22c, aurintricarboxylic acid, gliotoxin, amiloride | ||
|- | |- | ||
| Line 79: | Line 80: | ||
| style="padding: 5px 5px; background: #F5F5F5;" |Brefeldin A, geldenamycin, 17AAG | | style="padding: 5px 5px; background: #F5F5F5;" |Brefeldin A, geldenamycin, 17AAG | ||
|- | |- | ||
| style="padding: 5px 5px; background: #F5F5F5;" colspan=2|<small> Adapted from | | style="padding: 5px 5px; background: #F5F5F5;" colspan=2|<small> Adapted from Abzug MJ. The enteroviruses: problems in need of treatments. ''J Infect''. 2014;68(1):S108-S114<ref name="Abzug2014">{{cite journal|last1=Abzug|first1=Mark J.|title=The enteroviruses: Problems in need of treatments|journal=Journal of Infection|volume=68|year=2014|pages=S108–S114|issn=01634453|doi=10.1016/j.jinf.2013.09.020}}</ref></small> | ||
|} | |} | ||
Latest revision as of 15:00, 18 September 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
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Overview
Currently, there are no specific therapies targeting EV-D68. Although the management of enteroviruses in general is only supportive, the development of pharmacologic therapies has recently emerged. Immune globulin therapy has demonstrated clinical and laboratory benefit among some patients with enterovirus infection. Antiviral medications against enteroviruses, such as pleconaril, are currently being studied for patients with severe infections caused by other subtypes of enteroviruses.
Future or Investigational Therapies
Immune globulin
- Studies in neonates with enterovirus infection suggest a possible benefit of the administration of immune globulin[1][2], however, more studies need to be done do confirm the benefit of this treatment.
- The development of IVIg with high levels of enterovirus antibody has shown benefit in in vitro and mouse models studies for enterovirus subtype 71. However, this has not been studied for EV-D68.[3]
Antiviral Medication
- There are no antiviral medications that specifically target EV-D68 only. Instead, antiviral medications against enteroviruses in general are also believed to be able to successfully target EV-D68.
- Pleconaril has shown benefit among patients with severe life-threatening enterovirus infections. This antiviral drug prevents the attachment of the virus to the host cell and integration of its RNA to the host DNA.[4]
- The table shown below describes the possible targets for antiviral treatment against enterovirus infections.[5][6]
| Target | Antiviral Drugs |
|---|---|
| Protease 2A or 3C | Rupintrivir, Br-UTP, AG7088 derivative |
| Capsid binders | Pleconaril, Pirodavirb, pyridazinyl oxime ethersb (BTA-39c), pyridyl imidazolidinonesc; NF-449c, V-073 |
| RNA replication (2C and 3B protein) | Enviroxime, TTP-8307, vinylacetylene analogs, GW5074c, Benzimidazoles, N(6)-benzyladenosine, metrifudil |
| RNA-dependent RNA polymerase | 2′C–Me-cytidine, 4′-azidocytidine, 2′C-ME-adenosine, ribavirin, DTriP-22c, aurintricarboxylic acid, gliotoxin, amiloride |
| Proteins involved in replication & assembly | Brefeldin A, geldenamycin, 17AAG |
| Adapted from Abzug MJ. The enteroviruses: problems in need of treatments. J Infect. 2014;68(1):S108-S114[7] | |
References
- ↑ Marc Tebruegge & Nigel Curtis (2009). "Enterovirus infections in neonates". Seminars in fetal & neonatal medicine. 14 (4): 222–227. doi:10.1016/j.siny.2009.02.002. PMID 19303380. Unknown parameter
|month=ignored (help) - ↑ M. J. Abzug, H. L. Keyserling, M. L. Lee, M. J. Levin & H. A. Rotbart (1995). "Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin". Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 20 (5): 1201–1206. PMID 7620000. Unknown parameter
|month=ignored (help) - ↑ Rui-Yuan Cao, Jian-Feng Han, Tao Jiang, Xue Tian, Man Yu, Yong-Qiang Deng, E.-De Qin & Cheng-Feng Qin (2011). "In vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors". Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 51 (4): 246–249. doi:10.1016/j.jcv.2011.05.002. PMID 21641277. Unknown parameter
|month=ignored (help) - ↑ Rotbart, H. A.; Webster, A. D. (2001). "Treatment of Potentially Life-Threatening Enterovirus Infections with Pleconaril". Clinical Infectious Diseases. 32 (2): 228–235. doi:10.1086/318452. ISSN 1058-4838.
- ↑ Thibaut, Hendrik Jan; Leyssen, Pieter; Puerstinger, Gerhard; Muigg, Alexandra; Neyts, Johan; De Palma, Armando Mirko (2011). "Towards the design of combination therapy for the treatment of enterovirus infections". Antiviral Research. 90 (3): 213–217. doi:10.1016/j.antiviral.2011.03.187. ISSN 0166-3542.
- ↑ Hendrik Jan Thibaut, Armando M. De Palma & Johan Neyts (2012). "Combating enterovirus replication: state-of-the-art on antiviral research". Biochemical pharmacology. 83 (2): 185–192. doi:10.1016/j.bcp.2011.08.016. PMID 21889497. Unknown parameter
|month=ignored (help) - ↑ Abzug, Mark J. (2014). "The enteroviruses: Problems in need of treatments". Journal of Infection. 68: S108–S114. doi:10.1016/j.jinf.2013.09.020. ISSN 0163-4453.