Research ArticleCancer

Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth

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Science Translational Medicine  06 Mar 2019:
Vol. 11, Issue 482, eaau5612
DOI: 10.1126/scitranslmed.aau5612

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No holds Barr-ed for cancer treatment

Persistent latent infection with Epstein-Barr virus contributes to tumorigenesis in a variety of cancer types. The only viral protein that is consistently expressed in these tumors is Epstein-Barr nuclear antigen 1, which performs a variety of biological functions. To target this antigen, Messick et al. designed a series of chemical inhibitors and then tested them in vitro and in multiple mouse models of Epstein-Barr virus–associated cancer. The authors characterized the inhibitors using a variety of assays, examined the mechanism by which they work, and demonstrated preclinical effectiveness and suitable pharmacological properties, paving the way for further therapeutic development.

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