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HCV Viral Production Inhibited

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  • scarletpaolicchi
    http://www.scienced aily.com/ releases/ 2009/03/09031013 1118.htm Hepatitis C: Key Molecules That Inhibit Viral Production Identified ScienceDaily (Mar. 16,
    Message 1 of 3 , Mar 25, 2009
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      http://www.scienced aily.com/ releases/ 2009/03/09031013 1118.htm

      Hepatitis C: Key Molecules That Inhibit Viral Production Identified

      ScienceDaily (Mar. 16, 2009) — In a new study, led by Professor Donny Strosberg
      of Scripps Florida, researchers describe peptides (molecules of two or more
      amino acids) derived from the core protein of hepatitis C. The team found that
      these peptides inhibit not only dimerization of the core protein (the joining of
      two identical subunits), but also production of the actual virus itself.
      "We went for the simplest solution, taking a peptide from core to see if we
      could block the interaction, " Strosberg said, "and it did."
      The Problem with Hepatitis C
      With over 170 million people infected worldwide by HCV, new therapeutic
      strategies for HVC—a blood-borne disease that affects the liver—are urgently
      needed.
      But one of the critical problems in developing drugs for HCV is that it mutates
      at such prodigious rates. An RNA virus like hepatitis C can mutate at a rate
      estimated as high as one million times that of DNA viruses; in contrast, DNA
      viruses contain an enzyme (polymerase) that acts as something of a proof reader
      to ensure that newly transcribed DNA strands are the same as the original,
      helping to reduce mutations.
      "In one sense, the ongoing issue with hepatitis C is that there are still so
      very few drugs to treat the virus and very few tools to study it," Strosberg
      said. "We set out to develop new tools and to identify a new target – core, the
      capsid protein. By targeting the interactions of core with itself or other
      proteins, we could reduce the problem of rapid mutation not only because the
      core protein mutates significantly less, but also because mutations that would
      affect the interface between core and itself or other proteins would often be
      more likely to deactivate the virus, in contrast to mutations in viral enzymes
      which often lead to increased resistance to drugs."
      Recent efforts to develop therapeutic strategies against HCV have concentrated
      on designing inhibitors that target several of the 10 HCV proteins that comprise
      the virus, including mostly the non-structural proteins. However, as the study
      points out, the one HCV structural protein that has not been targeted yet is the
      core protein, the one responsible for assembly and packaging of the HCV RNA
      genome.
      The Core of the Matter
      Core, the most conserved protein among all HCV genotypes, plays several
      essential roles in the viral cycle in the host cell; studies have suggested that
      these core-core or core-other protein interactions can modulate various
      functions including signaling, apoptosis or programmed cell death, lipid
      metabolism, and gene transcription.
      The core protein is particularly important in the assembly of the hepatitis C
      nucleocapsid, an essential step in the formation of infectious viral particles;
      the nucleocapsid is the viral genome protected by a protein coat – the capsid.
      This core protein plays an essential role in the HCV cycle during assembly and
      release of the infectious virus, as well as disassembly of viral particles upon
      entering host cells.
      Looking closely at the core interaction with itself, Strosberg developed several
      novel quantitative assays or tests for monitoring these protein-protein
      interactions with the specific goal of identifying inhibitors of the core
      dimerization, which would block virus production.
      "People have been dreaming about inhibiting protein-protein interactions, as a
      new El Dorado for finding novel drug targets," says Strosberg, "but few
      conclusive studies have emerged, except in the virus-host area."
      Inhibition of HCV Production
      The new research, however, led to the discovery of two peptides that inhibited
      HCV production by 68 percent and 63 percent, respectively; a third related
      peptide showed 50 percent inhibition. When added to HCV-infected cells, each of
      the three peptides blocked release but not replication of infectious virus;
      viral RNA levels were reduced by seven fold. Strosberg notes that the efficacy
      of small molecules like these can often be improved over initial levels.
      "After we'd finished our work, we learned that Frank Chisari – one of the
      leading experts on HCV who works at Scripps Research in La Jolla – had been
      looking at similar peptides using a very different approach," said Strosberg.
      "One of his peptides was the same as ours – it also inhibited virus production.
      It's an incredible coincidence and a confirmation of our study."

      Best Wishes,
      Scarlet
      http://www.healthyhepper.com
    • Arkhepcgal@aol.com
      I have been trying to find the site to ask a question. I ve been negative for Hep C-genotype 2b since March 2004; was diagnosed with early cirrhosis in
      Message 2 of 3 , Mar 25, 2009
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        I have been trying to find the site to ask a question.

        I've been negative for Hep C-genotype 2b since March 2004; was diagnosed
        with early cirrhosis in February 1999. I was originally diagnosed with Hep C in
        November 1999, did the 3X interferon/ribivirin, went negative right away,
        but relapsed. I did the treatment again in November 2003 using Roche's
        interferon and copegus. I again went negative immediately and have been ever since.

        I've just had an ultrasound, cat scan and an MRI which show a large mass in
        my liver. The gastro doc doesn't seem to think it's cancer and my alpha-
        fetaprotein is negative. I now have to have a 'tri-basic' or 'tri-phase' (?)
        cat scan and I have an appointment to go to the University of Arkansas Medical
        facility in Little Rock at the end of May. (I live in the very northwest
        corner of Arkansas). I also have grade 3 varices along with GERD and Barrett's
        Disease that wreck havoc in my esophagus and get ulcers quite often.

        I know that the liver itself doesn't have pain, but the sheath/skin around
        it has nerves that can hurt. I've have 'deep', sharp aches directly
        underneath and along my rib cage on my right side which seem to be worse after I eat.
        At first I thought it was the ulcer, but now I'm not so sure.

        My question is: Since the liver can regenerate itself, could the docs be
        thinking of removing the side of the liver with the mass and that new,
        undiseased liver tissue will regrow?

        I can't seem to get a clear answer from the nurse and the appointment I have
        in Little Rock will be an assessment type of visit. If surgery is
        recommended, about how long will the recovery be, etc?

        I'm 62 and have over 20 diagnosed diseases/illnesses that I am fighting as
        well as the cirrhosis.

        Do you know of others that have had to have a mass removed and how they did
        after that?

        Thank you,

        Betty Kibat
        Arkhepcgal@...
        **************Great Deals on Dell 15" Laptops - Starting at $479
        (http://pr.atwola.com/promoclk/100126575x1220635228x1201407499/aol?redir=http:%2F%2Fad.doub
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        [Non-text portions of this message have been removed]
      • Doc
        ... diagnosed ... with Hep C in ... away, ... Roche s ... been ever since. ... mass in ... alpha- ... tri-phase (?) ... Arkansas Medical ... northwest ...
        Message 3 of 3 , Mar 31, 2009
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          --- In GIWorld-Hepatitis@yahoogroups.com, Arkhepcgal@... wrote:
          >
          > I have been trying to find the site to ask a question.
          >
          > I've been negative for Hep C-genotype 2b since March 2004; was
          diagnosed
          > with early cirrhosis in February 1999. I was originally diagnosed
          with Hep C in
          > November 1999, did the 3X interferon/ribivirin, went negative right
          away,
          > but relapsed. I did the treatment again in November 2003 using
          Roche's
          > interferon and copegus. I again went negative immediately and have
          been ever since.
          >
          > I've just had an ultrasound, cat scan and an MRI which show a large
          mass in
          > my liver. The gastro doc doesn't seem to think it's cancer and my
          alpha-
          > fetaprotein is negative. I now have to have a 'tri-basic' or
          'tri-phase' (?)
          > cat scan and I have an appointment to go to the University of
          Arkansas Medical
          > facility in Little Rock at the end of May. (I live in the very
          northwest
          > corner of Arkansas). I also have grade 3 varices along with GERD and
          Barrett's
          > Disease that wreck havoc in my esophagus and get ulcers quite often.
          >
          > I know that the liver itself doesn't have pain, but the sheath/skin
          around
          > it has nerves that can hurt. I've have 'deep', sharp aches directly
          > underneath and along my rib cage on my right side which seem to be
          worse after I eat.
          > At first I thought it was the ulcer, but now I'm not so sure.
          >
          > My question is: Since the liver can regenerate itself, could the
          docs be
          > thinking of removing the side of the liver with the mass and that
          new,
          > undiseased liver tissue will regrow?
          >
          > I can't seem to get a clear answer from the nurse and the appointment
          I have
          > in Little Rock will be an assessment type of visit. If surgery is
          > recommended, about how long will the recovery be, etc?
          >
          > I'm 62 and have over 20 diagnosed diseases/illnesses that I am
          fighting as
          > well as the cirrhosis.
          >
          > Do you know of others that have had to have a mass removed and how
          they did
          > after that?
          >
          > Thank you,
          >
          > Betty Kibat
          > Arkhepcgal@...
          > **************Great Deals on Dell 15" Laptops - Starting at $479
          >
          (http://pr.atwola.com/promoclk/100126575x1220635228x1201407499/aol?redir\
          =http:%2F%2Fad.doub
          > leclick.net%2Fclk%3B213153654%3B34689672%3Bo)
          >
          >
          > [Non-text portions of this message have been removed]
          >
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