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

Ila R. Singh1*, John E. Gorzynski1, Daria Drobysheva1, Leda Bassit2, Raymond F. Schinazi2 1 Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America, 2 Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia, United States of America.

 

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.

Citation: 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

Editor: Peter Sommer, Institut Pasteur Korea, Republic of Korea

 

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

Copyright: © 2010 Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work is supported in part by NIH grant 2P30-AI-50409 (CFAR to RFS), and by the Department of Veterans Affairs (RFS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: RFS is a founder and major shareholder of RFS Pharma, LLC that is developing Amdoxovir clinically and he receives royalties from the sales of 3TC. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

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

 

 See whole research study: http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0009948