Chikungunya: treatments, opportunities and possibilities
Joseph R Freitas A C , Shambhavi Rao B and Suresh Mahalingam A DA Institute for Glycomics, Griffith University (Gold Coast campus), Qld, Australia.
B National Institute of Virology, Pune, India. Tel: +91 8826472536, Email: shambhavi2536@gmail.com
C Tel: +61 7 5552 9351, Email: j.freitas@griffith.edu.au
D Tel: +61 7 5552 7178, Email: s.mahalingam@griffith.edu.au
Microbiology Australia 39(2) 76-79 https://doi.org/10.1071/MA18021
Published: 18 April 2018
Abstract
The natural progression of chikungunya virus (CHIKV) disease can consist of three stages – acute, post-acute and chronic, each having different clinical features. The acute phase (up to 3 weeks) is characterised by high viremia, fever, rash, polyarthralgia, synovitis and intense inflammation. Complete recovery is achieved in most symptomatic cases after this phase. However, in a large proportion of patients symptoms persist into a post-acute phase and in some may even continue to become chronic. In the post-acute phase, which can last up to 4 months, there is clinical persistence of joint inflammation or relapse after transient improvement. These can lead to musculoskeletal disorders and eventually chronicity of disease. The main symptoms being chronic inflammatory rheumatism that can last for several years in some cases. With the near global reach, debilitating nature and recent outbreaks of CHIKV there has been much research effort put towards combatting it. New antivirals and medications to counteract inflammation are being developed. Development of CHIKV vaccines is also an area with intense research focus.
References
[1] Burt, F.J. et al. (2012) Chikungunya: a re-emerging virus. Lancet 379, 662–671.| Chikungunya: a re-emerging virus.Crossref | GoogleScholarGoogle Scholar |
[2] Burt, F.J. et al. (2017) Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen. Lancet Infect. Dis. 17, e107–e117.
| Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXitVSqu7w%3D&md5=8bfa2cd668a80d4c00f12e45124d091aCAS |
[3] Helenius, A. et al. (1982) Inhibition of Semliki forest virus penetration by lysosomotropic weak bases. J. Gen. Virol. 58, 47–61.
| Inhibition of Semliki forest virus penetration by lysosomotropic weak bases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XhtFGmurs%3D&md5=dda3fb94c65fd49c9bd00d22bb73c634CAS |
[4] de Lamballerie, X. et al. (2009) Antiviral treatment of chikungunya virus infection. Infect. Disord. Drug Targets 9, 101–104.
| Antiviral treatment of chikungunya virus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlt1Krtb4%3D&md5=4613d0c8d96c155458463ce52ed10429CAS |
[5] Briolant, S. et al. (2004) In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination. Antiviral Res. 61, 111–117.
| In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXps1Grtb8%3D&md5=f9dcf2b642d13de913adf7d924781164CAS |
[6] Delogu, I. et al. (2011) In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant. Antiviral Res. 90, 99–107.
| In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmvFSkt74%3D&md5=f4dc4d71bef7251084d0686d1145f0f0CAS |
[7] Pohjala, L. et al. (2011) Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays. PLoS One 6, e28923.
| Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjvFSntw%3D%3D&md5=77126ff1987faee6489524effdab1eabCAS |
[8] Kaur, P. et al. (2013) Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob. Agents Chemother. 57, 155–167.
| Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXlt1SrsL4%3D&md5=9c82891e0a1d2cee0b21ef10cbc42d19CAS |
[9] Varghese, F.S. et al. (2016) Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res. 126, 117–124.
| Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XlvVOksw%3D%3D&md5=5265f7b0913d19042ae4974b1b557831CAS |
[10] Wang, Y.M. et al. (2016) Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission. Antiviral Res. 135, 81–90.
| Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhslShtbbI&md5=1d0ef9fba194a3de075f19d882b9c1ffCAS |
[11] Varghese, F.S. et al. (2017) Obatoclax inhibits alphavirus membrane fusion by neutralizing the acidic environment of endocytic compartments. Antimicrob. Agents Chemother. 61, e02227-16.
| Obatoclax inhibits alphavirus membrane fusion by neutralizing the acidic environment of endocytic compartments.Crossref | GoogleScholarGoogle Scholar |
[12] Chen, W. et al. (2017) Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation. Nat. Microbiol. 2, 1435–1445.
| Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhvV2isbzJ&md5=a23390cff133e8a7a591a91269718af6CAS |
[13] Herrero, L.J. et al. (2015) Pentosan polysulfate: a novel glycosaminoglycan-like molecule for effective treatment of alphavirus-induced cartilage destruction and inflammatory disease. J. Virol. 89, 8063–8076.
| Pentosan polysulfate: a novel glycosaminoglycan-like molecule for effective treatment of alphavirus-induced cartilage destruction and inflammatory disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtFyku7rN&md5=35612dd00080382dfd7a22c18e9917abCAS |
[14] Fric, J. et al. (2013) Use of human monoclonal antibodies to treat Chikungunya virus infection. J. Infect. Dis. 207, 319–322.
| Use of human monoclonal antibodies to treat Chikungunya virus infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXktFCrtQ%3D%3D&md5=17e655f1b5198dcd01c96037141149fdCAS |
[15] Broeckel, R. et al. (2017) Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques. PLoS Negl. Trop. Dis. 11, e0005637.
| Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.Crossref | GoogleScholarGoogle Scholar |
[16] Miner, J.J. et al. (2017) Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis. Sci. Transl. Med. 9, .
| Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC1cXivFWmsrs%3D&md5=4c390bdcc15884e4b6be5089f2c1ce8cCAS |
[17] Edelman, R. et al. (2000) Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218. Am. J. Trop. Med. Hyg. 62, 681–685.
| Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3jslGhtA%3D%3D&md5=f06ed354596a4847742bc62d83b25646CAS |
[18] Taylor, A. et al. (2017) Mutation of the N-terminal region of chikungunya virus capsid protein: implications for vaccine design. MBio 8, e01970-16.
| Mutation of the N-terminal region of chikungunya virus capsid protein: implications for vaccine design.Crossref | GoogleScholarGoogle Scholar |
[19] Gorchakov, R. et al. (2012) Attenuation of Chikungunya virus vaccine strain 181/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein. J. Virol. 86, 6084–6096.
| Attenuation of Chikungunya virus vaccine strain 181/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XnsVKnsbw%3D&md5=f1c132b0e7d989a9f050ff112f9a6d4fCAS |
[20] Plante, K. et al. (2011) Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. PLoS Pathog. 7, e1002142.
| Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVOrt73E&md5=a5d7f660118cf69c2bfb78b4302059a4CAS |
[21] Hallengärd, D. et al. (2014) Novel attenuated Chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice. J. Virol. 88, 2858–2866.
| Novel attenuated Chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice.Crossref | GoogleScholarGoogle Scholar |
[22] Lam, S. et al. (2015) A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis. MAbs 7, 1178–1194.
| A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XmvFyrtb8%3D&md5=553968fc2c001a9b88d6a86fc7de17a6CAS |
[23] Chang, L.J. et al. VRC 311 Study Team (2014) Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet 384, 2046–2052.
| Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlOrt7fJ&md5=aee636b42da3a3f3195eaeb18598e405CAS |
[24] NIH ( 2015) NIH-sponsored clinical trial of chikungunya vaccine opens.https://www.niaid.nih.gov/news-events/nih-sponsored-clinical-trial-chikungunya-vaccine-opens
[25] Sutter, G. and Staib, C. (2003) Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. Curr. Drug Targets Infect. Disord. 3, 263–271.
| Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnslyqsr8%3D&md5=ba9664a0d1b19fda5506f830e062ef7cCAS |
[26] van den Doel, P. et al. (2014) Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge. PLoS Negl. Trop. Dis. 8, e3101.
| Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.Crossref | GoogleScholarGoogle Scholar |
[27] Roques, P. et al. (2017) Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus. JCI Insight 2, e83527.
| Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus.Crossref | GoogleScholarGoogle Scholar |
[28] Knudsen, M.L. et al. (2015) Alphavirus replicon DNA expressing HIV antigens is an excellent prime for boosting with recombinant modified vaccinia Ankara (MVA) or with HIV gp140 protein antigen. PLoS One 10, e0117042.
| Alphavirus replicon DNA expressing HIV antigens is an excellent prime for boosting with recombinant modified vaccinia Ankara (MVA) or with HIV gp140 protein antigen.Crossref | GoogleScholarGoogle Scholar |
[29] Hallengärd, D. et al. (2014) Prime-boost immunization strategies against Chikungunya virus. J. Virol. 88, 13333–13343.
| Prime-boost immunization strategies against Chikungunya virus.Crossref | GoogleScholarGoogle Scholar |