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.
Keywords: alphavirus; antiviral; chikungunya; drug likeness; drug targets; pre-clinical validation.