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Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA

Authors

  • Raquel T. Lima,

    1. Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
    2. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
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    • These authors equally contributed to this work.
  • Hugo Seca,

    1. Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
    2. Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Porto, Portugal
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    • These authors equally contributed to this work.
  • Andreia Palmeira,

    1. Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
    2. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    3. Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
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  • Miguel X. Fernandes,

    1. Centro de Química da Madeira, Centro de Competência de Ciências Exactas e da Engenharia, University of Madeira, Funchal, Portugal
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  • Felipe Castro,

    1. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    2. Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
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  • Marta Correia-da-Silva,

    1. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    2. Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
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  • Maria S. J. Nascimento,

    1. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    2. Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Porto, Portugal
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  • Emília Sousa,

    1. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    2. Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
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  • Madalena Pinto,

    1. CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Porto, Portugal
    2. Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
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  • M. Helena Vasconcelos

    Corresponding author
    1. Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Porto, Portugal
    • Cancer Drug Resistance Group, IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
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Corresponding authors: M. Helena Vasconcelos, hvasconcelos@ipatimup.pt; E. Sousa, esousa@ff.up.pt

Abstract

Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad-spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub-sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti-EBV agents.

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