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Singh IR, Gorzynski JE, Drobysheva D, Bassit L, Schinazi RF (2010)

Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome.

PLoS ONE 5(4): e9948. doi:10.1371/journal.pone.0009948

Ila R. Singh(1,*), John E. Gorzynski(1), Daria Drobysheva(1), Leda Bassit(2), Raymond F. Schinazi(2)

1 Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America,

2 Center for AIDS Research, Laboratory of Biochemical Pharmacology, epartment of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia, United States of America

* E-mail: ila.singh@path.utah.edu

Received: February 18, 2010; Accepted: March 11, 2010; Published: April 1, 2010

Abstract

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.

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