chikungunya virus ( chikv ) is an arthropod - borne virus belonging to the family , togaviridae , and genus , alphavirus . in this group of 29 viruses , six cause arthralgia and arthritis upon infection in humans .
these six viruses are chikv , ross river virus ( rrv ) , semliki forest virus ( sfv ) , onyong - nyong virus ( onnv ) , sindbis virus ( sinv ) and mayaro virus ( mayv ) .
the name chikungunya means  that which bends up  and refers to the contorted posture adopted by infected patients .
symptomatic chikv infections are characterised by fever , rashes and arthralgia leading to arthritis . in the last 50 years
there have been frequent outbreaks of chikv disease in asia and africa . in 2005 - 2006
an outbreak that occurred in la runion island resulted in approximately 260,000 cases of chikv associated fever with 237 deaths reported2 .
additionally , in 2006 - 2007 around 1.5 million cases of chikv disease were reported in india3 . through viral adaptation chikv has broadened its vector competence and therefore increased its potential to cause human disease .
a single mutation , a226e in the envelope protein 1 ( e1 ) of chikv , now allows aedes albopictus as well as ae .
currently there are no vaccines or antivirals for the prevention or treatment of chikv infections .
treatment is symptomatic with analgesics , antipyretics and non - steroidal anti - inflammatory agents .
passive immunization with human iggs derived from chikv infected patients has been shown to be protective in mice against chikv challenge5 .
this approach may prove effective for the prevention and treatment of neonates who are at the risk of infection from viraemic mothers .
however , this is not cost - effective and it is critical to develop antiviral drugs and/or vaccines for the control of chikv infections .
owing to the recent outbreaks of chikv in asia , africa and la runion island there has been a renewed interest in the development of antiviral drugs and vaccines to manage chikv infections . in this article
, we report on the advancements made towards the development of anti - inflammatory agents , antivirals and vaccines for the efficient control of chikv infections .
chloroquine phosphate was reported to be effective in the treatment of chronic chikv arthritis6 . however , in a clinical trial of chloroquine in chikv infected patients , no difference was observed between the placebo group and the treatment group7 .
maheshwari et al8 have also reported that in a mouse model , chloroquine enhances alphavirus replication and aggravates disease pathogenesis .
ribavirin , an antiviral agent was used to treat chikv induced arthritis in a small cohort of patients and was found to be beneficial in resolving joint and soft tissue swelling9 .
briolant et al10 have reported a synergistic effect of ribavirin and interferon- in the inhibition of chikv and sfv replication in cell culture .
recently rulli et al11 have reported using bindarit , a small molecule anti - inflammatory drug , in a mouse model to effectively treat chikv induced arthritis .
an additional 356 compounds ( natural and clinically approved drugs ) were initially screened for their antiviral effects using a chikv replicon cell line13 . a recombinant chikv with rluc ( renilla luciferase ) fused with nonstructural protein 3 ( chikv - rluc ) was constructed and used to validate the most active compounds from the initial screening studies . out of 12 selected compounds , coumarin 30
was found to be the most potent in inhibiting the replication of chikv - rluc virus ( ic50 value of 6.4 m ) .
arbidol , licensed for the treatment of influenza and other respiratory infections , was found to be effective in inhibiting chikv replication in vero and mrc-5 cell lines ( ic50<10g / ml)14 .
recently , screening of a highly purified natural compound library for inhibition of chikv replication identified 44 inhibitors15 . among the selected compounds , harringtone , a cephalotoxine alkaloid ,
was found to be a potent inhibitor of chikv infection with an ec50 value of 0.24 m .
was also found to inhibit sinv replication suggesting the drug may be effective against other alphaviruses . in another study , an optimal homology model of chikv nonstructural protein 2(nsp2 )
based on the active site of nsp2 model , a virtual screening was performed with commercially available compounds subsequently 26 compounds were evaluated for the anti - chikv activity in a cell culture assay16 .
levitt et al17 described the development of an attenuated strain of chikv ( 181/25 ) obtained by serial passage in mrc-5 cells .
this vaccine candidate was tested in both mice and non - human primates and was found to protect the animals against challenge with parent virus . however , in phase ii trials the vaccine caused mild transient arthralgia in some of vaccinees18 .
recent attempts to develop a chikv vaccine have used formalin inactivated vaccine19 , virus like particles ( vlps)20 and dna vaccines2122 .
immunization with vlps and dna vaccines resulted in immunogenicity and protected the mice and non - human primates against subsequent challenge with chikv .
chimaeric viruses containing venezeulean equine encephalitis virus ( veev ) or eastern equine encephalitis virus ( eeev ) or sinv non - structural proteins with chikv structural proteins elicited neutralizing antibodies and protected the mice against chikv challenge23 . however , these viruses still had the ability to infect mosquitoes and attenuation was dependent on an intact interferon response in mice .
another chimaeric vaccine using veev strain tc-83 and encepahalomyocarditis virus ( emcv ) ires ( internal ribosome entry site ) in the subgenomic promoter was developed to reduce the transmission to mosquitoes .
recently chattopadhyay et al25 developed a chimaeric vaccine using a vesiculostomatitis virus ( vsv ) backbone and chikv structural proteins ( vsvg - chikv ) .
this vsvg - chikv chimaeric virus induced a good neutralizing antibody response and protected mice against chikv infection .
plante et al24 designed a vaccine by introducing the emcv ires sequence into the chikv subgenomic promoter .
this reduced the replication of the vaccine strain in mosquitoes and was highly immunogenic in mice .
sirnas and shrnas against envelope protein e1 , nsp3 , capsid and nsp1 proteins of the chikv have been used to inhibit the replication of chikv in mammalian cells with promising results2627 .
furthermore , in vivo studies have shown that shrna e1 offers a strong and sustained protection against chikv infection in suckling mice .
studies on the role of mannose binding lectin ( mbl ) in rrv - induced arthritis in mice28 suggest that mbl may be a target for therapeutic intervention in the treatment of alphavirus induced arthritis / myositis .
inhibitors targeting the mbl pathway of complement may be useful in the treatment of alphavirus induced diseases . additionally , a peptide corresponding to the autophagy inducing peptide , beclin , has been shown to be effective against chikv infections in cell culture and in mice29 .
a recent study on gene profiling has revealed a significant overlap of differentially expressed genes involved in the inflammatory processes of both chikv- induced arthritis and rheumatoid arthritis ( ra ) .
thus , new drugs being developed for ra might also be beneficial for the treatment of alphavirus induced arthritis30 .
chikungunya fever is a global health problem and several outbreaks have occurred in the last 50 years in asia and africa .
recent outbreaks in la runion and italy have raised the awareness of the need to develop effective antiviral drugs or vaccines against chikv .
although many antiviral compounds have been shown to be effective in cell culture , very few compounds have been evaluated in animal models .
intensive studies are needed to evaluate the effect of appropriate compounds in animal models and humans .
 chikungunya virus , a re - emerging mosquito - borne alphavirus , causes fever , rash and persistent arthralgia / arthritis in humans . 
 severe outbreaks have occurred resulting in infections of millions of people in southeast asia and africa . 
 currently there are no antiviral drugs or vaccines for prevention and treatment of chikungunya infections . 
 herein we report the current status of research on antiviral drugs and vaccines for chikungunya virus infections . 