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

被引:44
作者
Singh, Ila R. [1 ]
Gorzynski, John E. [1 ]
Drobysheva, Daria [1 ]
Bassit, Leda [2 ,3 ]
Schinazi, Raymond F. [2 ,3 ]
机构
[1] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA
[2] Emory Univ, Sch Med, Dept Pediat, Ctr AIDS Res,Lab Biochem Pharmacol, Decatur, GA 30033 USA
[3] Vet Affairs Med Ctr, Decatur, GA 30033 USA
来源
PLOS ONE | 2010年 / 5卷 / 03期
关键词
INTRAVENOUS IMMUNOGLOBULIN; CONTROLLED TRIAL; PREVALENCE; RETROVIRUS; RESISTANT; THERAPY; BLIND;
D O I
10.1371/journal.pone.0009948
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:7
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