1. Sulfated small molecules targeting eBV in Burkitt lymphoma: from in silico screening to the evidence of in vitro effect on viral episomal DNA
- Author
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Marta Correia-da-Silva, Felipe Castro, Miguel X. Fernandes, Maria São José Nascimento, Hugo Seca, Emília Sousa, Andreia Palmeira, M. Helena Vasconcelos, Raquel T. Lima, and Madalena Pinto
- Subjects
Herpesvirus 4, Human ,In silico ,Xanthones ,Antineoplastic Agents ,Biology ,medicine.disease_cause ,Biochemistry ,Antiviral Agents ,Virus ,Drug Delivery Systems ,hemic and lymphatic diseases ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Pharmacology ,Flavonoids ,Virtual screening ,Drug discovery ,Organic Chemistry ,DNA, Neoplasm ,medicine.disease ,Virology ,Epstein–Barr virus ,Burkitt Lymphoma ,In vitro ,Lymphoma ,Virus Latency ,Lytic cycle ,DNA, Viral ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Plasmids - 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 subsequently, 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.
- Published
- 2012