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PLoS ONE: Raltegrevir is a Potent Inhibitor of XMRV...

Discussion in 'XMRV Research and Replication Studies' started by parvofighter, Apr 1, 2010.

  1. citybug

    citybug Senior Member

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    Quote:
    A select number of antiviral agents known to inhibit viruses other than retroviruses were also evaluated. These included the anti-herpetic drugs acyclovir (ACV), ganciclovir (GCV), vidarabine (ara-A), 5-Iodo-2′-deoxyuridine (IdUrd), penciclovir (PCV), foscarnet (PFA), vistide (HPMPC); the anti-hepatitis drugs entecavir (ETV), telbivudine (LdT), and ribavirin (RBV). ETV was also selected because it was recently reported to inhibit HIV-1 replication, both in vitro and in humans [16]. Other compounds claimed to be effective against XMRV, MLV, HIV-1 and other viruses, such as chloroquine [17], dehydroepiandrosterone (DHEA) [18], methylene blue and aspirin were also evaluated for anti-XMRV activity in vitro. Methylene blue is known to have antiherpetic activity and also can inactivate HIV-1 [19]. Unfortunately, most of the compounds listed above, except IdUrd were ineffective against XMRV, or were effective at toxic concentrations (Figure 1). IdUrd demonstrated a low therapeutic index (TI, the ratio of CC50/EC50) and cannot be considered as a specific antiviral agent against XMRV.

    so antivirals didn't work. doesn't look like they checked artesunate.
  2. lululowry

    lululowry Senior Member

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    Anti-HIV drugs inhibit XMRV

    Four drugs used to treat HIV infection can inhibit a retrovirus recently linked to prostate cancer and chronic fatigue syndrome, researchers at Emory University/Atlanta Veterans Affairs Medical Center and the University of Utah have shown.

    The results were published on April 1, 2010 by the journal PLoS One.

    The findings suggest that if XMRV (xenotropic murine leukemia virus-related virus) is proven to be a cause for prostate cancer or chronic fatigue syndrome, those illnesses may be treatable with drugs already approved for treating HIV.

    Discovered in 2006, XMRV has been detected in some prostate cancer patients' tumor biopsies by several investigators. However, its precise role in driving prostate cancer is unclear. A recent report (from the Whittemore Peterson Institute in Nevada) detected XMRV in a majority of chronic fatigue syndrome patients, but these results have not been confirmed by other laboratories.

    "Not all studies that have looked for XMRV have been able to detect it in prostate cancers or in samples from chronic fatigue syndrome," says Ila Singh, MD, PhD, associate professor of pathology at the University of Utah School of Medicine. "We will need to see the results of clinical trials before these drugs can be used in a clinical setting."

    Singh and Raymond Schinazi, PhD, DSc, professor of pediatrics and chemistry at Emory's Center for AIDS Research and the Atlanta VAMC, and colleagues teamed up to test 45 anti-HIV compounds, some of these discovered by Emory researchers, and other antiviral compounds against XMRV in cell culture.

    The most potent drug against XMRV was raltegravir, produced by Merck and sold under the commercial name Isentress. The FDA initially approved raltegravir in 2007 only for persons whose HIV infection was resistant to other drugs, but in 2009 its approval was expanded to all HIV infected persons.

    Raltegravir represents a new class of antiretroviral drugs because it inhibits the integrase enzyme, preventing the virus from invading a cell's DNA. Other drugs against HIV inhibit either the reverse transcriptase enzyme, which copies the virus' genetic information, or the protease enzyme, which carves up newly produced viral proteins so that viruses can be assembled. However, none of the protease inhibitors inhibited XMRV in culture.

    Besides raltegravir, three other compounds - another integrase inhibitor and AZT and tenofovir DF, two reverse transcriptase inhibitors - also inhibit XMRV replication. This suggests that these drugs could be used together in combination therapy, a particularly effective tactic against HIV that helps prevent the emergence of drug-resistant forms of the virus.

    "Our study showed that these drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent cocktail' therapies might inhibit the virus from replicating and spreading," Schinazi says. "This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant."

    Although both XMRV and HIV are retroviruses, there is little similarity between HIV and XMRV at the protein level. Scientists have been able to show that several retroviruses cause cancer in animals, but only a few retroviruses are known to infect humans: human T-lymphotropic viruses 1 and 2, HIV, and now XMRV. Singh and Schinazi are now investigating the development of resistance in XMRV to raltegravir and other drugs.

    Singh led a recently published study that demonstrated the presence of XMRV in 27 percent of prostate cancers examined, with the virus more likely to be found in the most-aggressive tumors. XMRV may promote cancer by integrating into the host cell DNA and warping the cell's regulation of its own genes.

    Research supported by: Emory Center for AIDS Research and the Department of Veterans Affairs.
  3. natasa778

    natasa778 Senior Member

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    I'm also wondering about curcumin...
  4. citybug

    citybug Senior Member

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    What natural elements make up the integrase enzyme? Can we starve it? I think natural things are taken for protease inhibitors.
  5. lululowry

    lululowry Senior Member

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    XMRV research at Emory

    I am new to all of this and foggy-brained to boot. Thank you to the moderator who moved the press release to this thread. :Retro redface: I emailed Dr. Raymond Schinazi (mentioned in the Anti-HIV drug study) to ask about further research. He's at Emory and I'm not far from there. He wrote back to say "We are beginning to work using an animal model for XMRV. We will prove that the drugs we discovered work in an animal model before we can embark on studies in humans." As you'll see from his bio, he has a vested interest in pursuing XMRV work, along with scientific and humanitarian interests, which means, I hope, that they are moving on this post haste.


    Here's his bio:


    Raymond F. Schinazi, PhD, Hon DSc
    Professor of Pediatrics and Chemistry; Director, Laboratory of Biochemical Pharmacology, and Senior Research Career Scientist; Core Director, Emory's Center for AIDS Research, Emory University / Veterans Affairs Medical Center

    Dr. Raymond F. Schinazi is Professor of Pediatrics and Chemistry and Director of the Laboratory of Biochemical Pharmacology at Emory University. Professor Schinazi received his Ph.D. in Chemistry in 1976 from the University of Bath, England, and completed post-doctoral training in Pharmacology at Yale University and in Virology/Immunology at Emory University. He serves as the Senior Research Career Scientist at the Atlanta Department of Veterans Affairs and Director of the Pharmacology/Drug Discovery Core for the NIH-sponsored Emory University Center for AIDS Research (CFAR). Dr. Schinazi is the founder of several biotechnology companies focusing on antiviral drug discovery and development, including Pharmasset Inc., Triangle Pharmaceuticals (acquired by Gilead in 2003), Idenix Pharmaceuticals (51% acquired by Novartis in 2003), and RFS Pharma LLC (formed in Sept 2004). He has published over 420 peer-reviewed papers and 7 books, and holds more than 70 US patents. He is best known for his innovative and pioneering work on d4T (stavudine), 3TC (lamivudine), FTC (emtriva), D-D4FC (reverset), RCV (racivir), and DAPD (amdoxovir), drugs that are now approved by the FDA, or are at various stages of clinical development. His inventions now sell more than US$2.0 billion per year and more than 80% of the HIV infected individuals take at least one of the drugs he invented. Dr. Schinazi is on the editorial board of several journals, including Antimicrobial Agents and Chemotherapy, Antiviral Research, AIDS Reviews, Antiviral Chemistry and Chemotherapy and Antiviral Therapy. He is the founder of the highly successful HIV- and HEP-DART conferences. Dr. Schinazi is the recipient of numerous awards, including the Georgia Biomedical Industry Growth Award, the Bruce Witte Award, the 2006 Distinguished Scientist Award from the Hepatitis B Foundation, and two Merit Awards (10 year grants) from NIH-NIAID. In 2006, he received an honorary D.Sc. from Bath University for his research accomplishments in the field of HIV and biotechnology. He also served on the Presidential Commission on AIDS.
  6. Gemini

    Gemini Senior Member

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    lulu,

    thanks for posting the great, informative bio of Dr. Schinazi and for contacting him directly.

    gemini

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