Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.
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.


RESULTS
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.
Singh
Ila R
IR
Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America. ila.singh@path.utah.edu
Gorzynski
John E
JE
Drobysheva
Daria
D
Bassit
Leda
L
Schinazi
Raymond F
RF
D000998:Antiviral Agents; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015673:Fatigue Syndrome, Chronic / Q000821:virology*; D005260:Female; D017988:Gammaretrovirus / Q000187:drug effects*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D011471:Prostatic Neoplasms / Q000821:virology*; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D012192:Retroviridae Infections / Q000188:drug therapy*; D014412:Tumor Virus Infections / Q000188:drug therapy*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium