Broad-Spectrum Antiviral Therapeutics

DrakeDrake Acolyte
edited October 2011 in Tech & Games
Press Release: "New drug could cure nearly any viral infection" http://web.mit.edu/newsoffice/2011/antiviral-0810.html

The title of the press release is pretty bold, but the scientific article that the release is based upon seems solid.

Scientific Article: "Broad-Spectrum Antiviral Therapeutics" http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022572

The rational behind this research is basically combining parts of the innate virus recognition system with part of an effector that causes death in virus-infected cells. The fusion of these bypasses the usual high levels of regulation in the innate viral defense system in order to immediately kill infected cells and prevent spread of the virus. This treatment is potentially effective against all viruses with genomes made of RNA, since the fusion protein recognizes dsRNA that is typically produced during viral replication.

I can try to help people get through the paper (it takes a while to get used to the style) and answer questions or provide some background on the topic.

Comments

  • Darth BeaverDarth Beaver Meine Ehre heißt Treue
    edited October 2011
    My eyes look like road maps right now with all the red lines. So I am replying now so this thread shows up in my subscriptions. This might make and interesting topic for the podcast.
  • edited October 2011
    A successful lentivirus-induced cell apoptosis trial in vivo will impress me. They've tested DRACO against other +ssRNA viri but I notice they've not tested its efficacy in lymph tissue nor against infected memory cells. So in the meantime I'll regard name dropping HIV as a cynical attempt to accrue further funding, along with helping to fight the non-existent war against Ebola (bio)terror.

    I mean, really, even Aum Shinrikyo couldn't have pulled that off.
  • DrakeDrake Acolyte
    edited October 2011
    A successful lentivirus-induced cell apoptosis trial in vivo will impress me. They've tested DRACO against other +ssRNA viri but I notice they've not tested its efficacy in lymph tissue nor against infected memory cells. So in the meantime I'll regard name dropping HIV as a cynical attempt to accrue further funding, along with helping to fight the non-existent war against Ebola (bio)terror.

    I mean, really, even Aum Shinrikyo couldn't have pulled that off.

    I've been busy and don't have very much time to reply (I'll probably have more later this week), but I'll mention a few things.

    Gene therapy is great, but the FDA is still afraid of it. I think that permanently introducing these genes would only be useful in certain cases unless more levels of regulation are controlling their expression. I think that something like you mentioned would be incredibly impressive if it worked in humans, but that seems a long way off (probably not in our lifetimes). Their choice to focus on a more traditional delivery system is probably the best one for now. The use of cell-penetrating peptides is a basic delivery technique that leaves much more efficiency to be desired, but they work as a proof of principal and were good enough to increase the survival of mice when challenged with influenza. Lymph tissue isn't incredibly resistant to cell-penetrating peptides as far as I know. The authors didn't say that the treatment would be effective against HIV or Ebola (they only mention them briefly in the introduction to highlight the lack of broad-spectrum antivirals). I don't think this therapy would be effective against HIV, since I'm pretty sure that it doesn't produce dsRNA (only ssRNA and DNA-RNA hybrids). Ebola does produce some dsRNA during its replication, so the treatments might be effective against it.

    My first thought after reading your first sentence was "lentiviruses induce apoptosis all the time."
  • DrakeDrake Acolyte
    edited October 2011
    I looked up some more information on antiviral responses to HIV and found a recent paper about RIG-I (Retinoic acid-Inducible Gene 1) and HIV.
    Paper: RIG-I-Mediated Antiviral Signaling Is Inhibited in HIV-1 Infection by a Protease-Mediated Sequestration of RIG-I http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020501/?tool=pubmed

    One of the fusions in the Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) used in the Broad-Spectrum Antiviral Therapeutics paper contained RIG-I, so there is a possibility that DRACO could detect HIV (if you believe the paper linking HIV and RIG-I signalling). From what I've read, the evidence they provide does not show that RIG-I will recognize HIV RNA (especially in a way that would be effective for DRACO recognition). I'm not really sure how this paper was published in Journal of Virology in the first place, since there seems to be little proof of the actual mechanism and the observations don't seem to be physiologically relevant to HIV infection (I'll stop getting off-topic with this, unless someone is interested).

    TL/DR: The results in this paper seem to support the idea that DRACO wouldn't be effective in detecting HIV.
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