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SIGA Technologies, Inc. Message Board

  • easttennesseehillbilly easttennesseehillbilly May 18, 2013 8:32 AM Flag

    Question for AMLN or anyone else?

    AMLN,
    Those of us on this board know how ST-246 works. In layman terms, how does CMX001 work on the pox virus?

    Thanks in advance,

    Tennessee

    Sentiment: Strong Buy

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    • “how does CMX001 work on the pox virus?”

      CMX001 is basically Cidofovir with a hunk of fat stuck to it. The fat gets cut off of the Cidovir in the human body. (But, not in monkeys, but, that's another story!). The cidofovir is a wacked-out building-block of DNA, and so stops DNA production in many viruses that are based upon DNA (rather than RNA). Poxvirus is a DNA virus.

      For the techies: “Cidofovir is a monophosphate nucleotide analogue. After undergoing cellular phosphorylation to its diphosphate form, it competitively inhibits the incorporation of deoxycytidine triphosphate into viral DNA by viral DNA polymerase. Incorporation of the drug disrupts further chain elongation. Unlike nucleoside analogues such as acyclovir, cidofovir is not phosphorylated (and hence activated) by a viral kinase. Cidofovir demonstrates in vitro activity against a number of DNA viruses, including the herpesviruses, adenovirus, polyomavirus, papillomavirus, and poxvirus. Cidofovir also retains activity against thymidine kinase-negative herpes simplex virus (HSV) and UL97 phosphotransferase-negative CMV, which are mutant viruses resistant to acyclovir and ganciclovir. Clinical efficacy has been demonstrated rigorously only against CMV. Its clinical utility in infections caused by other viral pathogens remains to be determined.”

    • Cidofovir selectively inhibits DNA synthesis. Therefore it is potentially effective on all DNA viruses. CMX is a prodrug which is metabolized intracellularly to cidofovir.

      The metabolic pathway of prodrug- active metabolite has not been characterized. This deficiency in information is what has kept chimerix from being successful in establishing a surrogate endpoint for efficacy in treating smallpox.

      The idea is that cidofovir inhibits viral dna synthesis more than it inhibits human dna synthesis. But since it does alter a fundamental part of cell chemistry it has a high potential for adverse reactions. It is being used clinically in terminal illnesses as a drug of last resort.

      Variola is a DNA virus, as opposed to an RNA virus.

    • "how does CMX001 work on the pox virus?"

      Expect "babbling sarcasm" from AMLNFREAK,NWJ?

      Bottom line is: It does not work on poxes@
      Question should be: How is it designed to hopefully work,NWJ?

      IMO

      Sentiment: Strong Buy

 
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