Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome – Source: PloS One, Apr 1, 2010

[Note: See also a commentary on these findings published April 1, by Scientific American. See also a Salt Lake news video clip of lead investigator Dr. Ila Singh.]

Background: Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population.

Principal Findings: Forty-five compounds, including twenty-eight drugs approved for use in humans, were evaluated against XMRV replication in vitro.

• We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively.

• Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication.

• When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses.

Conclusions: If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials.

Source: PLOS One, Apr 1, 2010. DOI:10.1371/journal.pone.0009948, by Singh IR, Gorzynski JE, Drobysheva D, Bassit L, Schinazi R. Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia, USA. [E-mail: ila.singh@path.utah.edu]

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