Chikungunya future or investigational therapies
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Overview
Medical therapy for chikungunya infection is still limited to supportive care and focused on the decrease of symptoms. Antiviral agents are yet in different stages of testing or development. Other treatment options, such as chemotherapy that targets the molecular level of the chikungunya virus, are still under study.
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)