Biochemical and biophysical characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel inhibitor as a potential drug candidate

Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective therapeutics strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-polymerase RNA-dependent (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified and mapped to bind to the nsp4-CHIKV active site. The inhibitory activity of LabMol-309 was evaluated in cellular-based antiviral assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights biophysical features of nsP4-CHIKV and identified a new compound as a promising antiviral agent against CHIKV infection.