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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848589/ https://www.ncbi.nlm.nih.gov/pubmed/20376347 http://dx.doi.org/10.1371/journal.pone.0009948 |
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author | Singh, Ila R. Gorzynski, John E. Drobysheva, Daria Bassit, Leda Schinazi, Raymond F. |
author_facet | Singh, Ila R. Gorzynski, John E. Drobysheva, Daria Bassit, Leda Schinazi, Raymond F. |
author_sort | Singh, Ila R. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2848589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28485892010-04-07 Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome Singh, Ila R. Gorzynski, John E. Drobysheva, Daria Bassit, Leda Schinazi, Raymond F. PLoS One Research Article 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. Public Library of Science 2010-04-01 /pmc/articles/PMC2848589/ /pubmed/20376347 http://dx.doi.org/10.1371/journal.pone.0009948 Text en Singh et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Singh, Ila R. Gorzynski, John E. Drobysheva, Daria Bassit, Leda Schinazi, Raymond F. Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title | Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title_full | Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title_fullStr | Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title_full_unstemmed | Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title_short | Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome |
title_sort | raltegravir is a potent inhibitor of xmrv, a virus implicated in prostate cancer and chronic fatigue syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848589/ https://www.ncbi.nlm.nih.gov/pubmed/20376347 http://dx.doi.org/10.1371/journal.pone.0009948 |
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