Inhibition of chikungunya virus by picolinate that targets viral capsid protein

Abstract

The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1×10(-7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases.

Inhibition of Chikungunya virus by an adenosine analog targeting the SAM‐dependent nsP1 methyltransferase

“…Titer determination was performed with conventional plaque‐forming assay . Briefly, 10‐fold dilutions of different viral stocks were prepared in DMEM medium with 2% FBS and were used to infect cell monolayer for 1.5 h at 37 °C.…”

Surface Plasmon Resonance: A Boon for Viral Diagnostics

“…Subsequent reduction in the viral mRNA and viral load was confirmed by QRT-PCR. This study will pave the way for developing pyridine based antiviral thereupeutics particularly against alphavirus (Sharma et al, 2016).…”

Small Molecule Inhibitors Targeting Chikungunya Virus

“…Picolinic acid (PCA), a potent inhibitor of CHIKV, closely resembles the molecular structure of proline. The compound is capable of binding to the hydrophobic pocket of CHIKV capsid (Sharma et al 2016). Treatment with PCA results in a significant reduction in vRNA levels and infectious virus, suggesting possible inhibitory effects on viral disassembly, replication, or nucleocapsid assembly (Sharma et al 2016).…”