Cloroquina
A cloroquina é teoricamente efetiva contra o vírus da chikungunya por meio da inibição de enzimas virais, da prevenção de entrada de vírus, do comprometimento da maturação viral ou da melhora da resposta imunológica à infecção. Um antigo estudo-piloto aberto em 10 pacientes recebendo cloroquina por 20 semanas sugeriu uma melhora subjetiva e objetiva na maioria dos pacientes, incluindo diminuição na rigidez matinal e números mais baixos no Índice Articular de Ritchie (uma avaliação numérica de dor articular em pacientes com artrite reumatoide).[84]Brighton SW. Chloroquine phosphate treatment of chronic Chikungunya arthritis: an open pilot study. S Afr Med J. 1984 Aug 11;66(6):217-8.
http://www.ncbi.nlm.nih.gov/pubmed/6087474?tool=bestpractice.com
No entanto, um ensaio clínico intervencionista de 2008 baseado na comunidade entre mais de 500 pacientes não mostrou uma vantagem da cloroquina em relação ao meloxicam (um anti-inflamatório não esteroidal) para tratar a dor musculoesquelética inicial e a artrite após a infecção aguda.[85]De Lamballerie X, Boisson V, Reynier JC, et al. On chikungunya acute infection and chloroquine treatment. Vector Borne Zoonotic Dis. 2008 Dec;8(6):837-9.
http://www.ncbi.nlm.nih.gov/pubmed/18620511?tool=bestpractice.com
Um estudo placebo-controlado em 54 pacientes mostrou que pacientes recebendo cloroquina tiveram mais artralgia que pacientes recebendo placebo 200 dias após a ocorrência da infecção.[86]Chopra A, Saluja M, Venugopalan A. Effectiveness of chloroquine and inflammatory cytokine response in patients with early persistent musculoskeletal pain and arthritis following chikungunya virus infection. Arthritis Rheumatol. 2014 Feb;66(2):319-26.
https://onlinelibrary.wiley.com/doi/full/10.1002/art.38221
http://www.ncbi.nlm.nih.gov/pubmed/24504804?tool=bestpractice.com
Interferona
A interferona com vetor adenoviral injetado em camundongos tem um efeito preventivo contra artralgia quando usada até 24 horas após um teste de desafio com o vírus da chikungunya. Estudos in vitro também sugerem inibição da replicação viral em células Vero, uma ação sinergicamente potencializada pelo uso concomitante de ribavirina.[88]Dagley A, Ennis J, Turner JD, et al. Protection against Chikungunya virus induced arthralgia following prophylactic treatment with adenovirus vectored interferon (mDEF201). Antiviral Res. 2014 Aug;108:1-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101997
http://www.ncbi.nlm.nih.gov/pubmed/24833276?tool=bestpractice.com
[89]Briolant S, Garin D, Scaramozzino N, et al. In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination. Antiviral Res. 2004 Feb;61(2):111-7.
http://www.ncbi.nlm.nih.gov/pubmed/14670584?tool=bestpractice.com
Outras terapias
Existem várias outras terapias sendo desenvolvidas, incluindo umifenovir, 6-azauridina, decanoil-RVKR-CMK, 5,7 di-hidroxiflavonas, harringtonina, ácido micofenólico, clorpromazina, ácido poli-inosínico policitidílico, ácido ribonucleico (RNA) interferente pequeno e trigocherrierin A.[89]Briolant S, Garin D, Scaramozzino N, et al. In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination. Antiviral Res. 2004 Feb;61(2):111-7.
http://www.ncbi.nlm.nih.gov/pubmed/14670584?tool=bestpractice.com
[90]Delogu I, Pastorino B, Baronti C, et al. In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant. Antiviral Res. 2011 Jun;90(3):99-107.
http://www.ncbi.nlm.nih.gov/pubmed/21440006?tool=bestpractice.com
[91]Ozden S, Lucas-Hourani M, Ceccaldi PE, et al. Inhibition of Chikungunya virusinfection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein. J Biol Chem. 2008 Aug 8;283(32):21899-908.
http://www.ncbi.nlm.nih.gov/pubmed/18559340?tool=bestpractice.com
[92]Pohjala L, Utt A, Varjak M, et al. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays. PLoS One. 2011;6(12):e28923.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242765
http://www.ncbi.nlm.nih.gov/pubmed/22205980?tool=bestpractice.com
[93]Kaur P, Thiruchelvan M, Lee RC, et al. Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother. 2013 Jan;57(1):155-67.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535938
http://www.ncbi.nlm.nih.gov/pubmed/23275491?tool=bestpractice.com
[94]Khan M, Dhanwani R, Patro IK, et al. Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells. Antiviral Res. 2011 Jan;89(1):1-8.
http://www.ncbi.nlm.nih.gov/pubmed/21070810?tool=bestpractice.com
[95]Lee RC, Hapuarachchi HC, Chen KC, et al. Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. PLoS Negl Trop Dis. 2013;7(2):e2050.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567007
http://www.ncbi.nlm.nih.gov/pubmed/23409203?tool=bestpractice.com
[96]Li YG, Siripanyaphinyo U, Tumkosit U, et al. Poly (I:C), an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells. Virol J. 2012 Jun 14;9:114.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490739
http://www.ncbi.nlm.nih.gov/pubmed/22698190?tool=bestpractice.com
[97]Parashar D, Paingankar MS, Kumar S, et al. Administration of E2 and NS1 siRNAs inhibit chikungunya virusreplication in vitro and protects mice infected with the virus. PLoS Negl Trop Dis. 2013 Sep 5;7(9):e2405.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764232
http://www.ncbi.nlm.nih.gov/pubmed/24040429?tool=bestpractice.com
[98]Dash PK, Tiwari M, Santhosh SR, et al. RNA interference mediated inhibition of Chikungunya virus replication in mammalian cells. Biochem Biophys Res Commun. 2008 Nov 28;376(4):718-22.
http://www.ncbi.nlm.nih.gov/pubmed/18805396?tool=bestpractice.com
[99]Bourjot M, Leyssen P, Neyts J, et al. Trigocherrierin A, a potent inhibitor of chikungunya virus replication. Molecules. 2014 Mar 24;19(3):3617-27.
https://www.mdpi.com/1420-3049/19/3/3617/htm
http://www.ncbi.nlm.nih.gov/pubmed/24662077?tool=bestpractice.com
No entanto, esses medicamentos estão somente nos primeiros estágios dos estudos clínicos. Os estudos para a descoberta de medicamentos estão se concentrando nos inibidores de replicação viral e na inibição da proteína de choque térmico HSP90, nas quinases e em outras vias de sinalização celular.[10]Burt FJ, Chen W, Miner JJ, et al. Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen. Lancet Infect Dis. 2017 Apr;17(4):e107-17.
http://www.ncbi.nlm.nih.gov/pubmed/28159534?tool=bestpractice.com
Imunoterapias existentes, como fingolimode, abatacepte e tofacitinibe, também estão sendo estudadas.[100]Teo TH, Chan YH, Lee WW, et al. Fingolimod treatment abrogates chikungunya virus-induced arthralgia. Sci Transl Med. 2017 Feb 1;9(375):eaal1333.
http://www.ncbi.nlm.nih.gov/pubmed/28148838?tool=bestpractice.com
[101]Miner JJ, Cook LE, Hong JP, et al. Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis. Sci Transl Med. 2017 Feb 1;9(375):eaah3438.
http://www.ncbi.nlm.nih.gov/pubmed/28148840?tool=bestpractice.com