Chikungunya future or investigational therapies: Difference between revisions
Jump to navigation
Jump to search
| Line 94: | Line 94: | ||
|+ | |+ | ||
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|}} | ! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|}} | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Furin inhibitors}} | ! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Furin inhibitors<ref>{{Cite journal | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|2',5'-Oligoadenylate | | author = [[Simona Ozden]], [[Marianne Lucas-Hourani]], [[Pierre-Emmanuel Ceccaldi]], [[Ajoy Basak]], [[Menogh Valentine]], [[Suzanne Benjannet]], [[Josee Hamelin]], [[Yves Jacob]], [[Kamel Mamchaoui]], [[Vincent Mouly]], [[Philippe Despres]], [[Antoine Gessain]], [[Gillian Butler-Browne]], [[Michel Chretien]], [[Frederic Tangy]], [[Pierre-Olivier Vidalain]] & [[Nabil G. Seidah]] | ||
| title = Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein | |||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Cellular IMPDH enzyme}} | | journal = [[The Journal of biological chemistry]] | ||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Viperin}} | | volume = 283 | ||
| issue = 32 | |||
| pages = 21899–21908 | |||
| year = 2008 | |||
| month = August | |||
| doi = 10.1074/jbc.M802444200 | |||
| pmid = 18559340 | |||
}}</ref>}} | |||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|2',5'-Oligoadenylate synthetase (OAS3)<ref>{{Cite journal | |||
| author = [[Anne-Claire Brehin]], [[Isabelle Casademont]], [[Marie-Pascale Frenkiel]], [[Cecile Julier]], [[Anavaj Sakuntabhai]] & [[Philippe Despres]] | |||
| title = The large form of human 2',5'-Oligoadenylate Synthetase (OAS3) exerts antiviral effect against Chikungunya virus | |||
| journal = [[Virology]] | |||
| volume = 384 | |||
| issue = 1 | |||
| pages = 216–222 | |||
| year = 2009 | |||
| month = February | |||
| doi = 10.1016/j.virol.2008.10.021 | |||
| pmid = 19056102 | |||
}}</ref>}} | |||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Cellular IMPDH enzyme<ref>{{Cite journal | |||
| author = [[M. Khan]], [[R. Dhanwani]], [[I. K. Patro]], [[P. V. L. Rao]] & [[M. M. Parida]] | |||
| title = Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells | |||
| journal = [[Antiviral research]] | |||
| volume = 89 | |||
| issue = 1 | |||
| pages = 1–8 | |||
| year = 2011 | |||
| month = January | |||
| doi = 10.1016/j.antiviral.2010.10.009 | |||
| pmid = 21070810 | |||
}}</ref>}} | |||
! style="background: #4479BA; width: 160px;" | {{fontcolor|#FFF|Viperin<ref>{{Cite journal | |||
| author = [[Terk-Shin Teng]], [[Suan-Sin Foo]], [[Diane Simamarta]], [[Fok-Moon Lum]], [[Teck-Hui Teo]], [[Aleksei Lulla]], [[Nicholas K. W. Yeo]], [[Esther G. L. Koh]], [[Angela Chow]], [[Yee-Sin Leo]], [[Andres Merits]], [[Keh-Chuang Chin]] & [[Lisa F. P. Ng]] | |||
| title = Viperin restricts chikungunya virus replication and pathology | |||
| journal = [[The Journal of clinical investigation]] | |||
| volume = 122 | |||
| issue = 12 | |||
| pages = 4447–4460 | |||
| year = 2012 | |||
| month = December | |||
| doi = 10.1172/JCI63120 | |||
| pmid = 23160199 | |||
}}</ref>}} | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;" |Assays | | style="padding: 5px 5px; background: #DCDCDC;" |Assays | ||
Revision as of 19:55, 18 June 2014
|
Chikungunya Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Chikungunya future or investigational therapies On the Web |
|
American Roentgen Ray Society Images of Chikungunya future or investigational therapies |
|
Risk calculators and risk factors for Chikungunya future or investigational therapies |
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[8] | 2',5'-Oligoadenylate synthetase (OAS3)[9] | Cellular IMPDH enzyme[10] | Viperin[11] | ||
|---|---|---|---|---|---|
| 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.
- ↑ Simona Ozden, Marianne Lucas-Hourani, Pierre-Emmanuel Ceccaldi, Ajoy Basak, Menogh Valentine, Suzanne Benjannet, Josee Hamelin, Yves Jacob, Kamel Mamchaoui, Vincent Mouly, Philippe Despres, Antoine Gessain, Gillian Butler-Browne, Michel Chretien, Frederic Tangy, Pierre-Olivier Vidalain & Nabil G. Seidah (2008). "Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein". The Journal of biological chemistry. 283 (32): 21899–21908. doi:10.1074/jbc.M802444200. PMID 18559340. Unknown parameter
|month=ignored (help) - ↑ Anne-Claire Brehin, Isabelle Casademont, Marie-Pascale Frenkiel, Cecile Julier, Anavaj Sakuntabhai & Philippe Despres (2009). "The large form of human 2',5'-Oligoadenylate Synthetase (OAS3) exerts antiviral effect against Chikungunya virus". Virology. 384 (1): 216–222. doi:10.1016/j.virol.2008.10.021. PMID 19056102. Unknown parameter
|month=ignored (help) - ↑ M. Khan, R. Dhanwani, I. K. Patro, P. V. L. Rao & M. M. Parida (2011). "Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells". Antiviral research. 89 (1): 1–8. doi:10.1016/j.antiviral.2010.10.009. PMID 21070810. Unknown parameter
|month=ignored (help) - ↑ Terk-Shin Teng, Suan-Sin Foo, Diane Simamarta, Fok-Moon Lum, Teck-Hui Teo, Aleksei Lulla, Nicholas K. W. Yeo, Esther G. L. Koh, Angela Chow, Yee-Sin Leo, Andres Merits, Keh-Chuang Chin & Lisa F. P. Ng (2012). "Viperin restricts chikungunya virus replication and pathology". The Journal of clinical investigation. 122 (12): 4447–4460. doi:10.1172/JCI63120. PMID 23160199. Unknown parameter
|month=ignored (help)