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

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 (...

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Veröffentlicht in:Chemical biology & drug design 2013-05, Vol.81 (5), p.631-644
Hauptverfasser: Lima, Raquel T., Seca, Hugo, Palmeira, Andreia, Fernandes, Miguel X., Castro, Felipe, Correia-da-Silva, Marta, Nascimento, Maria S. J., Sousa, Emília, Pinto, Madalena, Vasconcelos, M. Helena
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Sprache:eng
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Zusammenfassung: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. The compounds: did not greatly affect cellular viability; decresed EBV DNA load; and reduced LMP1 protein expression.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.12109