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 (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.
Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Raquel T
RT
Lima
Hugo
H
Seca
Andreia
A
Palmeira
Miguel X
MX
Fernandes
Felipe
F
Castro
Marta
M
Correia-da-Silva
Maria S J
MS
Nascimento
Emília
E
Sousa
Madalena
M
Pinto
M Helena
MH
Vasconcelos
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000821:virology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004279:DNA, Viral / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D010957:Plasmids / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D017735:Virus Latency / Q000187:drug effects; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004273:DNA, Neoplasm; D004279:DNA, Viral; D005419:Flavonoids; D044004:Xanthones