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Structure-function insights into chikungunya virus capsid protein: Small molecules targeting capsid hydrophobic pocket.

Abstract

The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses. Molecular contacts between CP-cdE2 were determined by fitting structures of CHIKV CP and cdE2 into the cryo-EM map of Venezuelan equine encephalitis virus (VEEV). Binding of (S)-(+)-Mandelic acid (MDA) and Ethyl 3-aminobenzoate (EAB) to the hydrophobic pocket of CP was evaluated by molecular docking. Surface plasmon resonance (SPR) and fluorescence spectroscopy experiments confirmed MDA and EAB binding to the CP. The binding constants (KD) obtained from SPR for MDA and EAB were 1.2 × 10-3 M and 0.2 × 10-9 M, respectively. This study adds to the understanding of chikungunya virus structural proteins and may serve as the basis for antiviral development against chikungunya disease.

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  • Authors+Show Affiliations

    ,

    Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.

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    Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.

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    Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.

    Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India. Electronic address: shailfbt@iitr.ac.in.

    Source

    Virology 515: 2018 02 pg 223-234

    MeSH

    Antiviral Agents
    Capsid
    Capsid Proteins
    Chikungunya Fever
    Chikungunya virus
    Humans
    Hydrophobic and Hydrophilic Interactions
    Kinetics
    Mandelic Acids
    Molecular Docking Simulation
    Protein Domains
    meta-Aminobenzoates

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    29306785