Chikungunya future or investigational therapies: Difference between revisions
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! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|}} | ! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|}} | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|}} | ! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Furin inhibitors}} | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|}} | ! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|2',5'-Oligoadenylate | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|}} | synthetase (OAS3)}} | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|}} | ! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Cellular IMPDH enzyme}} | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Viperin}} | |||
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| style="padding: 5px 5px; background: #DCDCDC;" | | | style="padding: 5px 5px; background: #DCDCDC;" |Assays | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |In vitro (myoblast cells) | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Human epithelial HeLa cell lines | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |In vitro (vero cells) | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |In vivo (monocytes) | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | | | style="padding: 5px 5px; background: #DCDCDC;" |Target/effectors | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Intracellular furin-mediated cleavage of viral envelope glycoproteins: the E2E3 or p62 precursor | ||
| style="padding: 5px 5px; background: #F5F5F5;" |Affects CHIKV replication through a RNase L-dependent pathway | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Depletion of intracellular guanosine pool | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Endoplasmic reticulum | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | | | style="padding: 5px 5px; background: #DCDCDC;" |Advantages | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Able to induce a stronger inhibition of viral infection. | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Ability of OAS3 to inhibit alphavirus growth may be important for the development of antiviral molecules against CHIKV | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |CHIKV utilizes IMPDH activity for its growth and multiplication which is a potential and effective target to | ||
prevent its infection | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Critical antiviral host protein that controls CHIKV infection and provides a preclinical basis for the design of effective control strategies against CHIKV. | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" | | | style="padding: 5px 5px; background: #DCDCDC;" |Disadvantages | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Not tested in ''invivo'' system | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Cannot rule out the possibility that OAS3-mediated inhibition of CHIKV was also due to a block early in virus life cycle, for example, viral entry and uncoating of virus particles | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |It would be useful to explore similar findings by targeting IMPDH in case of other alphaviruses which are more lethal than chikungunya like Sindbis virus, Semliki forest virus, and so forth | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" |Large gaps in our understanding of the precise mechanisms at play for viperin to exert such a wide variety of roles within the cell | ||
|- | |- | ||
| style="padding: 5px 5px; background: #FFF;" colspan="6"| <SMALL>Table adapted from Antiviral Perspectives for Chikungunya Virus<ref name="ParasharCherian2014">{{cite journal|last1=Parashar|first1=Deepti|last2=Cherian|first2=Sarah|title=Antiviral Perspectives for Chikungunya Virus|journal=BioMed Research International|volume=2014|year=2014|pages=1–11|issn=2314-6133|doi=10.1155/2014/631642}}</ref></SMALL> | | style="padding: 5px 5px; background: #FFF;" colspan="6"| <SMALL>Table adapted from Antiviral Perspectives for Chikungunya Virus<ref name="ParasharCherian2014">{{cite journal|last1=Parashar|first1=Deepti|last2=Cherian|first2=Sarah|title=Antiviral Perspectives for Chikungunya Virus|journal=BioMed Research International|volume=2014|year=2014|pages=1–11|issn=2314-6133|doi=10.1155/2014/631642}}</ref></SMALL> | ||
Revision as of 19:42, 18 June 2014
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Overview
Major Tested Anti-Chikungunya Chemical Compounds
| Chloroquine[1][2] | Ribavirin[3] | 6-Azauridine[4] | Arbidol[5] | Harringtonine[6] | |
|---|---|---|---|---|---|
| Assay type | In vitro (vero cells) | Human | In vitro (vero cells) | In vitro (vero and primary human fibroblast cells) | In vitro (BHK21 cells) |
| Hypothesized target | Disrupted endosome-mediated Chikungunya internalization, possibly through the prevention of endosomal acidification. | Can interact with the intracellular viral RNA production. | Inhibition of orotidine monophosphate decarboxylase, an enzyme involved in the de novo biosynthesis of pyrimidine, cytidine, and thymidine. | Inhibition of virus mediated fusion and blocking of the viral entry into the target cells through inhibition of glycoprotein conformational changes that are essential for the fusion process. | Affects Chikungunya RNA production inside the infected cell as well as viral protein expression such as the nsP3 and the E2 proteins. |
| Advantages | In vitro study proved that it blocks the production of proinflammatory cytokines and the proliferation of
monocytes, macrophages, and lymphocytes |
Faster resolution of joint and soft tissue manifestations. | Showed a significant inhibition of Chikungunya at a low concentration. | Well-tolerated with minimal side effects | Minimal cytotoxicity |
| Disadvantages | In vivo study required. | Involvement of a small number of patients and lack of planning as randomly distributed patients were not
compared with a placebo group. |
The antiviral activity has been difficult to replicate in vivo. | Not tested in in vivo system. | Not tested in in vivo system. |
| Table adapted from Antiviral Perspectives for Chikungunya Virus[7] | |||||
Major Cellular Inhibitors Against Chikungunya Virus
| Furin inhibitors | 2',5'-Oligoadenylate
synthetase (OAS3) |
Cellular IMPDH enzyme | Viperin | ||
|---|---|---|---|---|---|
| Assays | In vitro (myoblast cells) | Human epithelial HeLa cell lines | In vitro (vero cells) | In vivo (monocytes) | |
| Target/effectors | Intracellular furin-mediated cleavage of viral envelope glycoproteins: the E2E3 or p62 precursor | Affects CHIKV replication through a RNase L-dependent pathway | Depletion of intracellular guanosine pool | Endoplasmic reticulum | |
| Advantages | Able to induce a stronger inhibition of viral infection. | Ability of OAS3 to inhibit alphavirus growth may be important for the development of antiviral molecules against CHIKV | CHIKV utilizes IMPDH activity for its growth and multiplication which is a potential and effective target to
prevent its infection |
Critical antiviral host protein that controls CHIKV infection and provides a preclinical basis for the design of effective control strategies against CHIKV. | |
| Disadvantages | Not tested in invivo system | Cannot rule out the possibility that OAS3-mediated inhibition of CHIKV was also due to a block early in virus life cycle, for example, viral entry and uncoating of virus particles | It would be useful to explore similar findings by targeting IMPDH in case of other alphaviruses which are more lethal than chikungunya like Sindbis virus, Semliki forest virus, and so forth | Large gaps in our understanding of the precise mechanisms at play for viperin to exert such a wide variety of roles within the cell | |
| Table adapted from Antiviral Perspectives for Chikungunya Virus[7] | |||||
References
- ↑ Khan, Mohsin; Santhosh, S.R.; Tiwari, Mugdha; Lakshmana Rao, P.V.; Parida, Manmohan (2010). "Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against chikungunya virus in vero cells". Journal of Medical Virology. 82 (5): 817–824. doi:10.1002/jmv.21663. ISSN 0146-6615.
- ↑ Delogu, Ilenia; de Lamballerie, Xavier (2011). "Chikungunya disease and chloroquine treatment". Journal of Medical Virology. 83 (6): 1058–1059. doi:10.1002/jmv.22019. ISSN 0146-6615.
- ↑ Rajan Ravichandran & Manju Manian (2008). "Ribavirin therapy for Chikungunya arthritis". Journal of infection in developing countries. 2 (2): 140–142. PMID 19738340.
- ↑ S. Briolant, D. Garin, N. Scaramozzino, A. Jouan & J. M. Crance (2004). "In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination". Antiviral research. 61 (2): 111–117. PMID 14670584. Unknown parameter
|month=ignored (help) - ↑ Ilenia Delogu, Boris Pastorino, Cecile Baronti, Antoine Nougairede, Emilie Bonnet & Xavier de Lamballerie (2011). "In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant". Antiviral research. 90 (3): 99–107. doi:10.1016/j.antiviral.2011.03.182. PMID 21440006. Unknown parameter
|month=ignored (help) - ↑ Parveen Kaur, Meerra Thiruchelvan, Regina Ching Hua Lee, Huixin Chen, Karen Caiyun Chen, Mah Lee Ng & Justin Jang Hann Chu (2013). "Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression". Antimicrobial agents and chemotherapy. 57 (1): 155–167. doi:10.1128/AAC.01467-12. PMID 23275491. Unknown parameter
|month=ignored (help) - ↑ 7.0 7.1 Parashar, Deepti; Cherian, Sarah (2014). "Antiviral Perspectives for Chikungunya Virus". BioMed Research International. 2014: 1–11. doi:10.1155/2014/631642. ISSN 2314-6133.