Sulfated small molecules targeting EBV in Burkitt lymphoma

Um trabalho multidisciplinar, combinando o screening virtual de uma biblioteca de pequenas moléculas com estudos de atividade anti-EBV numa linha celular de Linfoma de Burkitt, colocou em evidência uma nova classe de moléculas que diminuem os níveis de EBV nesta linha celular. Apesar de serem necessários mais estudos para validar a possibilidade destes compostos serem considerados antivirais para o EBV, esta descoberta poderá ser um ponto de partida para a posterior obtenção de outros compostos com modificações na estrutura química, de forma a ser conseguida uma melhoria da respetiva potência. Será também importante validar a função destes compostos noutras linhas celulares de Linfoma de Burkitt ou mesmo noutros modelos de cancro associados ao EBV.

Authors and affiliations:

Raquel T. Lima1,2; Hugo Seca1,3; Andreia Palmeira1,2,4; Miguel X. Fernandes5; Felipe Castro2,4; Marta Correia-da-Silva2,4; Maria São José Nascimento2,3; Emília Sousa2,4; Madalena Pinto2,4;M. HelenaVasconcelos1,3

1Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal.

2CEQUIMED-UP, Centre of Medicinal Chemistry – University of Porto, Portugal

3 Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Portugal.

4Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal

5Centro de Química da Madeira, Centro de Competência de Ciências Exactas e da Engenharia, University of Madeira, Portugal.

Abstract:

Sulfated small molecules targeting EBV in Burkitt lymphoma: from in silico screening to the evidence of in vitro effect on viral episomal DNA

EBV infects more than 90% of the world population. Following primary infection, EBV 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. The present work identified three novel sulfated small molecules capable of decreasing EBV levels in a Burkitt lymphoma cell line. Therefore, the in silico screening presents a good approach for the development of new anti-EBV agents.

Journal:

Chemical Biology & Drug Design

Link:

http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12109/pdf