Chikungunya virus (CHIKV) infection is one of the most challenging human Arboviral infections with global significance and without any specific antiviral. In this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT) was synthesised as a molecular hybrid of 2-methyl benzimidazole and isatin-β-thiosemicarbazone and its anti-CHIKV property was evaluated. The release of infectious virus particles was calculated by plaque assay, expression profile of viral RNA was estimated by RT-PCR and viral protein profiles were assessed by Western blot and FACS analyses. The safety index of MBZM-N-IBT was found to be >21. The CHIKV infectious viral particle formation was abrogated around 76.02% by MBZM-N-IBT during infection in mammalian system and the viral RNA synthesis was reduced by 65.53% and 23.71% for nsP2 and E1 respectively. Surprisingly, the viral protein levels were reduced by 97% for both nsP2 and E2. In the time-of-addition experiment it abrogated viral infection at early as well as late phase of viral life cycle, which indicates about multiple mechanisms for its anti-CHIKV action.In silicoanalysis justified development of MBZM-N-IBT with good affinities for potential target proteins of CHIKV and related virus. With predictions of good drug-likeness property, it shows potential of a drug candidate which needs further experimental validation.

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.

The challenges of viral infection have increased in recent decades due to the emergence of resistance, cross-resistance and drying up of antiviral drug discovery. Many neglected tropical viruses including the chikungunya virus, dengue virus & Japanese encephalitis virus have gradually become global pathogens. This has further increased the burden of viral infection which necessitates the continuous development of antiviral therapy. The antiviral chemistry began with the development of thiosemicarbazide derived thiosemicarbazones as antiviral. Although very few thiosemicarbazides have progressed into clinical application, it still inspires antiviral development. During last 3 decades (1990- 2020), several efforts have been made to develop suitable antiviral by using thiosemicarbazide scaffold. Its hybridization with other pharmacophores has been used as a strategy to enhance safety and efficacy. Cyclization and substitution of thiosemicarbazides have also been used to develop potent antiviral. With the ability to form coordinate bonds, thiosemicarbazides have been used either as metal complex or chelator against viruses. This work is an attempt to systematically review the research on the use of thiosemicarbazides as an antiviral scaffold. It also reviews the structure-activity relationship and translational suitability of thiosemicarbazide derived compounds.

Chikungunya virus (CHIKV) has reemerged as a global public health threat. The inflammatory pathways of the renin-angiotensin system (RAS) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) are usually involved in viral infections.