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Title: Inhibition of chikungunya virus by picolinate that targets viral capsid protein
Authors: Sharma R.
Fatma B.
Saha A.
Bajpai S.
Sistla S.
Dash P.K.
Parida M.
Kumar, Pravindra R.Manish
Tomar, Shailly
Published in: Virology
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. © 2016 Elsevier Inc.
Citation: Virology(2016), 498(): 265-276
Issue Date: 2016
Publisher: Academic Press Inc.
Keywords: Antiviral
Capsid protein
Chikungunya virus
Picolinic acid
Protein-protein interactions
Pyridine ring, Surface Plasmon resonance
Quantitative real-time RT-PCR
ISSN: 426822
Author Scopus IDs: 57209347974
Author Affiliations: Sharma, R., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India
Fatma, B., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India
Saha, A., Division of Virology, Defence Rese
Funding Details: ST acknowledges the financially support from Defence Research and Development Establishment (DRDE) Proj. No. DRDE/TC/05414/sub-Project/DRD-203/01/16 . Department of Biotechnology (DBT) is acknowledged by RS for his Senior Research Fellowship (SRF). We tha
Corresponding Author: Tomar, S.; Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email:
Appears in Collections:Journal Publications [BT]

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