Chikungunya epidemiological survey and Current available inhibitors

Surender Singh Jadav, Praveen Korupolu, Barij Nayan Sinha, Venkatesan Jayaprakash


Chikungunya is an insect borne disease virus spread through the mosquitoes to humans, causes the severe joint pains. The recent 2005-2007 outbreak was the most severe and one of the biggest eruptions caused by this virus. The cases of virus have been reported across the globe which was initially transmitted from African subcontinent, after its first outbreak in 1952 in Tanzania. Cause of disease remains to be explore and not well known. The complete epidemiology, mode of treatment and current research scenario through scientific literature on current CHIKV inhibitors was made to understand the in depth background of this disease. The current review posses the brief epidemiology, clinical manifestations, current mode of treatment and the number of antiviral agents (natural & synthetic) available up to date against the CHIKV infections along with vaccine development.


Chikungunya; epidemiology; Antiviral therapy

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Mohan, A., Chikungunya fever: clinical manifestations & management. Ind J Med Res 2006, 124, 471-474.

Mohan, A., Chikungunya fever strikes in Andhra Pradesh. All India Institute of Medical Sciences, New Delhi: 2006.

Simon, F.; Savini, H.; Parola, P., Chikungunya: a paradigm of emergence and globalization of vector-borne diseases. Med Clin North Am 2008, 92, 1323-1343.

Sudeep, A.; Parashar, D., Chikungunya: an overview. J Biosci 2008, 33, 443-449.

Chevillon, C.; Briant, L.; Renaud, F.; Devaux, C., The Chikungunya threat: an ecological and evolutionary perspective. Trends Microbiol 2008, 16, 80-88.

Pialoux, G.; Gazre, B.-A.; Jaurguiberry, S.; Strobel, M., Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007, 7, 319-327.

Powers, A. M.; Logue, C. H., Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. J Gen Virol 2007, 88, 2363-2377.

Krishnamoorthy, K.; Harichandrakumar, K.; Krishna Kumari, A.; Das, L., Burden of chikungunya in India: estimates of disability adjusted life years (DALY) lost in 2006 epidemic. J Vector Borne Dis 2009, 46, 26-35.

Lumsden, W., An epidemic of virus disease in Southern Province, Tanganyika territory, in 19521953 II. General description and epidemiology. Trans Royal Soc Trop Med Hyg 1955, 49, 33-57.

Monath, T. P., The arboviruses: epidemiology and ecology. . CRC Press, Inc.: 1989; Vol. 5.

Nimmannitya, S.; Halstead, S. B.; Cohen, S. N.; Margiotta, M. R., Dengue and chikungunya virus infection in man in Thailand, 1962-1964. I. Observations on hospitalized patients with hemorrhagic fever. Am J Trop Med Hyg 1969, 18, 954-71.

GIBBS Jr, C., Virological Investigation of the Epidemic of Haemorrhagic Fever in Calcutta: Isolation of Three Strains of Chikungunya Virus. Ind J Med Res 1964, 52, 676-683.

Padbidri, V.; Gnaneswar, T., Epidemiological investigations of chikungunya epidemic at Barsi, Maharashtra state, India. J Hyg Epidemiol Microbiol Immmunol 1978, 23, 445-451.

Sergon, K.; Njuguna, C.; Kalani, R.; Ofula, V.; Onyango, C.; Konongoi, L. S.; Bedno, S.; Burke, H.; Dumilla, A. M.; Konde, J., Seroprevalence of chikungunya virus (CHIKV) infection on Lamu Island, Kenya, October 2004. Am J Trop Med Hyg 2008, 78, 333-337.

Sergon, K.; Yahaya, A. A.; Brown, J.; Bedja, S. A.; Mlindasse, M.; Agata, N.; Allaranger, Y.; Ball, M. D.; Powers, A. M.; Ofula, V., Seroprevalence of Chikungunya virus infection on Grande Comore Island, union of the Comoros, 2005. Am J Trop Med Hyg 2007, 76, 1189-1193.

Chretien, J.-P.; Linthicum, K. J., Chikungunya in Europe: what's next? The Lancet 2007, 370, 1805-1806.

Njenga, M. K.; Nderitu, L.; Ledermann, J.; Ndirangu, A.; Logue, C.; Kelly, C.; Sang, R.; Sergon, K.; Breiman, R.; Powers, A., Tracking epidemic chikungunya virus into the Indian Ocean from East Africa. J Gen Virol 2008, 89, 2754-2760.

Arankalle, V. A.; Shrivastava, S.; Cherian, S.; Gunjikar, R. S.; Walimbe, A. M.; Jadhav, S. M.; Sudeep, A.; Mishra, A. C., Genetic divergence of Chikungunya viruses in India (19632006) with special reference to the 20052006 explosive epidemic. J Gen Virol 2007, 88, 1967-1976.

Sang, R. C.; Ahmed, O.; Faye, O.; Kelly, C. L.; Yahaya, A. A.; Mmadi, I.; Toilibou, A.; Sergon, K.; Brown, J.; Agata, N., Entomologic investigations of a chikungunya virus epidemic in the Union of the Comoros, 2005. Am J Trop Med Hyg 2008, 78, 77-82.

Borgherini, G.; Poubeau, P.; Staikowsky, F.; Lory, M.; Le Moullec, N.; Becquart, J. P.; Wengling, C.; Michault, A.; Paganin, F., Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clin Infect Dis 2007, 44, 1401-1407.

Ramful, D.; Carbonnier, M.; Pasquet, M.; Bouhmani, B.; Ghazouani, J.; Noormahomed, T.; Beullier, G.; Attali, T.; Samperiz, S.; Fourmaintraux, A., Mother-to-child transmission of Chikungunya virus infection. Pediatr Infect Dis J 2007, 26, 811-815.

Reiter, P.; Fontenille, D.; Paupy, C., Aedes albopictus as an epidemic vector of chikungunya virus: another emerging problem? Lancet Infect Dis 2006, 6, 463-464.

Vazeille, M.; Moutailler, S.; Coudrier, D.; Rousseaux, C.; Khun, H.; Huerre, M.; Thiria, J.; Dehecq, J.-S.; Fontenille, D.; Schuffenecker, I., Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus. PLoS One 2007, 2, e1168.

Tsetsarkin, K. A.; Vanlandingham, D. L.; McGee, C. E.; Higgs, S., A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathogens 2007, 3, e201.

Dash, P.; Parida, M.; Santhosh, S.; Verma, S.; Tripathi, N.; Ambuj, S.; Saxena, P.; Gupta, N.; Chaudhary, M.; Babu, J. P., East Central South African genotype as the causative agent in reemergence of Chikungunya outbreak in India. Vector-Borne Zoonot 2007, 7, 519-528.

Angelini, R.; Finarelli, A.; Angelini, P.; Po, C.; Petropulacos, K.; Macini, P.; Fiorentini, C.; Fortuna, C.; Venturi, G.; Romi, R., An outbreak of chikungunya fever in the province of Ravenna, Italy. Euro Surveill 2007, 12, E070906.

Lanciotti, R. S.; Kosoy, O. L.; Laven, J. J.; Panella, A. J.; Velez, J. O.; Lambert, A. J.; Campbell, G. L., Chikungunya virus in US travelers returning from India, 2006. Emerg Infect Dis 2007, 13, 764.

Knudsen, A. B., Global distribution and continuing spread of Aedes albopictus. Parassitologia 1995, 37, 91.

Gratz, N., Critical review of the vector status of Aedes albopictus. Med Vet Entomol 2004, 18, 215-227.

Strauss, J. H.; Strauss, E. G., The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 1994, 58, 491.

Singh, S. K.; Unni, S. K., Chikungunya virus: host pathogen interaction. Rev Med Virol 2011, 21, 78-88.

Staikowsky, F.; Le Roux, K.; Schuffenecker, I.; Laurent, P.; Grivard, P.; Develay, A.; Michault, A., Retrospective survey of Chikungunya disease in Reunion Island hospital staff. Epidemiol Infect 2008, 136, 196-206.

Taubitz, W.; Cramer, J. P.; Kapaun, A.; Pfeffer, M.; Drosten, C.; Dobler, G.; Burchard, G. D.; Lscher, T., Chikungunya fever in travelers: clinical presentation and course. Clin Infec Dis 2007, 45, e1-e4.

Thiruvengadam, K.; Kalyanasundaram, V.; Rajgopal, J., Clinical and pathological studies on chikungunya fever in Madras city. Ind J Med Res 1965, 53, 729-744.

Win, M.; Chow, A.; Dimatatac, F.; Go, C.; Leo, Y., Chikungunya fever in Singapore: acute clinical and laboratory features, and factors associated with persistent arthralgia. J Clin Virol 2010, 49, 111-114.

Powers, A. M., Chikungunya. Clin Lab Med 2010, 30, 209-219.

Bernard, E.; Solignat, M.; Gay, B.; Chazal, N.; Higgs, S.; Devaux, C.; Briant, L., Endocytosis of chikungunya virus into mammalian cells: role of clathrin and early endosomal compartments. PLoS One 2010, 5, e11479.

Weaver, S. C.; Reisen, W. K., Present and future arboviral threats. Antivir Res 2010, 85, 328-345.

Brighton, S.; Prozesky, O.; De La Harpe, A., Chikungunya virus infection: A retrospective study of 107 cases. SA Med J 1983, 63, 313-315.

Schmaljohn, A. L.; McClain, D., Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae). The University of Texas Medical Branch at Galveston: 1996.

McGill, P. E., Viral infections: ?-viral arthropathy. Bailliere's Clin Rheumatol 1995, 9, 145-150.

Staples, J. E.; Breiman, R. F.; Powers, A. M., Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis 2009, 49, 942-948.

Kalantri, S.; Joshi, R.; Riley, L. W., Chikungunya epidemic: an Indian perspective. Natl Med J Ind 2006, 19, 315.

Takehara, M. N., Mayumi; Sardjito, R., Inhibitory effect of concanavalin A on Chikungunya virus growth and infectivity. In ICMR Annals, 1982; Vol. 2, pp 97-103.

Pohjala, L.; Alakurtti, S.; Ahola, T.; Yli-Kauhaluoma, J.; Tammela, P., Betulin-derived compounds as inhibitors of alphavirus replication. J Nat Prod 2009, 72, 1917-1926.

FRESNO, M.; JIMNEZ, A.; VZQUEZ, D., Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem 1977, 72, 323-330.

Bourjot, M.; Delang, L.; Nguyen, V. H.; Neyts, J.; Guritte, F. o.; Leyssen, P.; Litaudon, M., Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of Chikungunya virus replication. J Nat Prod 2012, 75, 2183-2187.

Allard, P.-M.; Martin, M.-T. r. s.; Tran Huu Dau, M.-E.; Leyssen, P.; Guritte, F.; Litaudon, M., Trigocherrin A, the first natural chlorinated daphnane diterpene orthoester from Trigonostemon cherrieri. Org Lett 2011, 14, 342-345.

Allard, P.-M.; Leyssen, P.; Martin, M.-T.; Bourjot, M.; Dumontet, V.; Eydoux, C.; Guillemot, J.-C.; Canard, B.; Poullain, C.; Guritte, F., Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri. Phytochem 2012, 84, 160-168.

Kaur, P.; Chu, J. J. H., Chikungunya virus: An update on antiviral development and challenges. Drug Disc Today 2013.

Rashad, A. A.; Keller, P. A., Structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins. J Mol Graph Model 2013, 44, 241-252.

Corlay, N.; Delang, L.; Girard-Valenciennes, E.; Neyts, J.; Clerc, P.; Smadja, J.; Guritte, F.; Leyssen, P.; Litaudon, M., Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication. Fitoterapia 2014.

Nothias-Scaglia, L.-F. l.; Retailleau, P.; Paolini, J.; Pannecouque, C.; Neyts, J.; Dumontet, V.; Roussi, F.; Leyssen, P.; Costa, J.; Litaudon, M., Jatrophane Diterpenes as Inhibitors of Chikungunya Virus Replication: StructureActivity Relationship and Discovery of a Potent Lead. J Nat Prod 2014.

Thiberville, S.-D.; Moyen, N.; Dupuis-Maguiraga, L.; Nougairede, A.; Gould, E. A.; Roques, P.; de Lamballerie, X., Chikungunya fever: Epidemiology, clinical syndrome, pathogenesis and therapy. Antivir Res 2013, 99, 345-370.

Savarino, A.; Cauda, R.; Cassone, A., On the use of chloroquine for chikungunya. Lancet Infect Dis 2007, 7, 633.

Rashad, A. A.; Mahalingam, S.; Keller, P. A., Chikungunya Virus: Emerging Targets and New Opportunities for Medicinal Chemistry. J Med Chem 2014, 57, 1147-1166.

Richter, M.; Nietzsche, S.; Bogner, E.; Wutzler, P.; Schmidtke, M., A viable Human Influenza A Virus Lacking Neuraminidase (NA) Activity-isolation and Characterization. Antivir Res 2011, 90, A52.

Crotty, S.; Maag, D.; Arnold, J. J.; Zhong, W.; Lau, J. Y.; Hong, Z.; Andino, R.; Cameron, C. E., The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med 2000, 6, 1375-1379.

Briolant, S.; Garin, D.; Scaramozzino, N.; Jouan, A.; Crance, J., In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-? and ribavirin combination. Antivir Res 2004, 61, 111-117.

Khan, M.; Dhanwani, R.; Patro, I.; Rao, P.; Parida, M., Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells. Antivir Res 2011, 89, 1-8.

Boriskin, Y. S.; Pcheur, E.-I.; Polyak, S. J., Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection. Virol J 2006, 3, 4.

Delogu, I.; Pastorino, B.; Baronti, C.; Nougairde, A.; Bonnet, E.; de Lamballerie, X., < i> In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant. Antivir Res 2011, 90, 99-107.

Pohjala, L.; Utt, A.; Varjak, M.; Lulla, A.; Merits, A.; Ahola, T.; Tammela, P., Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays. PloS One 2011, 6, e28923.

Stringfellow, D. A., Comparation interferon-inducing and antiviral properties of 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), tilorone hydrochloride, and polyinosinic-polycytidylic acid. Antimicrob Agents Chemother 1977, 11, 984-992.

Bassetto, M.; De Burghgraeve, T.; Delang, L.; Massarotti, A.; Coluccia, A.; Zonta, N.; Gatti, V.; Colombano, G.; Sorba, G.; Silvestri, R., Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antivir Res 2013, 98, 12-18.

Cruz, D. J. M.; Bonotto, R. M.; Gomes, R. G.; da Silva, C. T.; Taniguchi, J. B.; No, J. H.; Lombardot, B.; Schwartz, O.; Hansen, M. A.; Freitas-Junior, L. H., Identification of Novel Compounds Inhibiting Chikungunya Virus-Induced Cell Death by High Throughput Screening of a Kinase Inhibitor Library. PLoS Neglect Trop Dis 2013, 7, e2471.

Eckels, K. H.; Harrison, V. R.; Hetrick, F. M., Chikungunya virus vaccine prepared by Tween-ether extraction. Appl Microbiol 1970, 19, 321-325.

Harrison, V.; Eckels, K.; Bartelloni, P.; Hampton, C., Production and evaluation of a formalin-killed Chikungunya vaccine. J Immunol 1971, 107, 643-647.

Levitt, N. H.; Ramsburg, H. H.; Hasty, S. E.; Repik, P. M.; Cole Jr, F. E.; Lupton, H. W., Development of an attenuated strain of chikungunya virus for use in vaccine production. Vaccine 1986, 4, 157-162.

Edelman, R.; Tacket, C.; Wasserman, S.; Bodison, S.; Perry, J.; Mangiafico, J., Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218. Am J Trop Med Hyg 2000, 62, 681-685.

Wang, E.; Volkova, E.; Adams, A. P.; Forrester, N.; Xiao, S.-Y.; Frolov, I.; Weaver, S. C., Chimeric alphavirus vaccine candidates for chikungunya. Vaccine 2008, 26, 5030-5039.

Muthumani, K.; Lankaraman, K. M.; Laddy, D. J.; Sundaram, S. G.; Chung, C. W.; Sako, E.; Wu, L.; Khan, A.; Sardesai, N.; Kim, J. J., Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus. Vaccine 2008, 26, 5128-5134.

Tiwari, M.; Parida, M.; Santhosh, S.; Khan, M.; Dash, P. K.; Rao, P., Assessment of immunogenic potential of Vero adapted formalin inactivated vaccine derived from novel ECSA genotype of Chikungunya virus. Vaccine 2009, 27, 2513-2522.

Plante, K.; Wang, E.; Partidos, C. D.; Weger, J.; Gorchakov, R.; Tsetsarkin, K.; Borland, E. M.; Powers, A. M.; Seymour, R.; Stinchcomb, D. T., Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism. PLoS Pathogens 2011, 7, e1002142.

Mallilankaraman, K.; Shedlock, D. J.; Bao, H.; Kawalekar, O. U.; Fagone, P.; Ramanathan, A. A.; Ferraro, B.; Stabenow, J.; Vijayachari, P.; Sundaram, S. G., A DNA vaccine against chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates. PLoS Neglect Trop Dis 2011, 5, e928.

Singh, P.; Chhabra, M.; Mittal, V.; Sharma, P.; Rizvi, M. A.; Chauhan, L. S.; Rai, A., Current research and clinical trials for a vaccine against Chikungunya virus. Vaccine: Dev Ther 2013, 3.




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