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Desintegration of retroviruses by metal chelating agents

Discussion in 'XMRV Testing, Treatment and Transmission' started by natasa778, Apr 20, 2010.

  1. natasa778

    natasa778 Senior Member

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    Few interesting abstracts and links. Apologies if this has been discussed here already.


    Disintegration of retroviruses by chelating agents
    Exposurein vitro of various mammalian retroviruses to the chelating agents EDTA or EGTA in millimolar concentrations resulted in partial disintegration of viral membranes as measured by accessibility or even release of reverse transcriptase, an internal viral protein, without any other treatment usually required. Among the viruses responding to chelators were mammalian type C viruses, primate type D viruses and bovine leukemia virus. The effect was dose-dependent. The avian type C virus AMV, however, was found to be not susceptible to the agents. Rauscher mouse leukemia virus treatedin vitro with EDTA or EGTA showed reduced infectivity in mice. The results are considered as evidence for some association of divalent cations with membranes of mammalian retroviruses. The disintegrating activity of EGTA suggests that Ca2+ is an integral constituent of viruses but Mg2+ may also be involved. These cations seem to be responsible for maintaining integrity of retroviral membranes which, after chelation of ions, are either disrupted or become permeable for the exogenous template of reverse transcriptase. In addition, the distintegrating activity of trifluoperazine may indicate that a calmodulin-like protein occurs in retroviral membranes. V. Wunderlich1 and G. Sydow1(1)Central Institute for Cancer Research, Robert-Rssle-Institute, Academy of Sciences of the German Democratic Republic, Berlin, German Democratic Republic. Received: 1 March 1982 Accepted: 2 April 1982


    Metal chelation underlies anti-HIV integrase activity of beta-diketo acids [no abstract] http://www.accessmylibrary.com/coms2/summary_0286-803606_ITM


    Patent: DMPS as antiHIV treatment: http://www.freepatentsonline.com/5464869.html


    Metal chelators as potential antiviral agents.
    Metal-chelating compounds can inhibit virus-induced enzymes in infected cells by coordinating with metal ions at their active sites. Consideration of the coordinating properties of ligands can explain the antiviral activity of these compounds. The antiviral actions of a number of compounds (e.g., thiosemicarbazones, pyrophosphate analogues, beta-diketones, cyclic polyethers and flavanoids) are discussed in the light of their metal-chelating properties. Hutchinson DW.Antiviral Res. 1985 Aug;5(4):193-205

    Inhibition of Tat-mediated HIV-1-LTR transactivation and virus replication by sulfhydryl compounds with chelating properties
    D-Penicillamine, a structural analog of cysteine, has the ability to chelate metal ions and reacts with cysteine. We have shown earlier that D-Penicillamin is a potential inhibitor of tat-mediated transactivation of HIV-1-LTR (14) and posesses anti-HIV-1 activity (23). Following this approach, we evaluated the anti-tat and anti-HIV-1 activity of several sulfhydryl compounds with chelating properties. The tested compounds: N-(2-Mercapto-propionyl)-glycin (MPG), 2,3-Dimercapto-propanol (DMP) and 2,3-Dimercapto-propane-sulfonic acid (DMPS) exhibited an inhibitory effect on the tat-mediated transactivation in Jurkat cells, as well as in U937 cells. The highest inhibitory response was shown by DMP leading to about 50% inhibition of transactivation in Jurkat cels and an 80% inhibition in U937 cells. On the contrary, DMPS (30 pg/ml) had no inhibitory effect in U937 cells, but did exhibit a 50% inhibition of transactivation in Jurkat cells at 30 μg/ml. The antiviral activity of DMP and DMPS was evaluated in H9 cells. In the concentration range which is effective for antiviral effect, both the compounds were highly cytotoxic. Mercapto-propionyl-glycin, although a weak inhibitor of transactivation, was able to inhibit synctia formation to more than 90% and inhibit the viral antigene expression to about 70%. The concentration of MPG needed to achieve this antiviral effect was very high, but it had no cytotoxicity at this concentration. We suggest that a search for compounds using this approach may be useful in developing potential inhibitors of tat-mediated transactivation. DEMIRHAN Ilhan et al (2) Department of Biochemistry, The George Washington University Medical Center, Washington, D.C., ETATS-UNIS


    Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin.
    Replication of human immunodeficiency virus type 1 (HIV-1) can be influenced by iron. Hence, decreasing the availability of iron may inhibit HIV-1 replication. Deferoxamine and deferiprone, both forming catalytically inactive iron-chelator complexes, and bleomycin, by use of which iron catalyzes oxidative nucleic acid destruction, were investigated. Expression of p24 antigen in human monocyte-derived macrophages and peripheral blood lymphocytes (PBL) was reduced by all 3 iron chelators. In PBL, p24 reduction was mirrored by a decrease in proliferation after incubation with deferoxamine or deferiprone, suggesting that viral inhibition is closely linked to a decrease in cellular proliferation. In contrast, clinically relevant bleomycin concentrations reduced p24 levels by approximately 50% without affecting proliferation. When deferoxamine and the nucleoside analogue dideoxyinosine were used in combination, they acted synergistically in inhibiting HIV-1 replication. These observations suggest that iron chelators with different mechanisms of action could be of additional benefit in antiretroviral combination therapy. Georgiou NA, et al Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. n.georgiou@lab.azu.nl J Infect Dis. 2000 Feb;181(2):484-90. PMID: 10669330


    Antiviral and immunomodulatory effects of desferrioxamine in cytomegalovirus-infected rat liver allografts with rejection.
    BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. METHOD: One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. RESULTS: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. CONCLUSIONS: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.PMID: 10609953 [PubMed - indexed for MEDLINE] Martelius T, et al. Department of Surgery, Helsinki University Hospital, Finland. Transplantation. 1999 Dec 15;68(11):1753-61


    Effect of desferrioxamine B, a metal chelating agent, on rhabdovirus multiplication.
    It has been suggested that the antiviral activity shown by chelating agents towards different viruses is probably related to the action on viral nucleic acid polymerases which require metal ions as essential cofactors. Desferrioxamine B, a metabolite from Streptomyces pilosus which chelates ions (Fe3+, Al3+, Cu2+, Zn2+, Co2+) from intracellular and external compartments, has been tested for its activity on the multiplication of VSV and rabies virus in CER cells. While desferrioxamine B was ineffective on rabies virus multiplication, it was shown to reduce plaque formation, cytopathic effect and viral yield by VSV at both low and high multiplicity of infection. The activity of the drug was not due to a direct action on virions outside the cells, but was probably related to an alteration in the delicate balance of intracellular ions which could in turn be critical for VSV multiplication. Conti C,et al Istituto di Microbiologia, Facolt di Medicina e Chirurgia, Universit di Roma La Sapienza. Boll Ist Sieroter Milan. 1990 Jun;69(2):431-6
  2. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I think this is interesting. Thanks for posting Natasa. May tie into autism/mercury link and why chelation had some positive results. Could it be that ME sufferers who improved on chelation did so, not because they were suffering from chronic mercury poisoning, but because of viral inhibition. Can anyone comment or elucidate further.

    The only time I seemed to improve significantly was after I had undergone 3mths Cutler protocol based around ALA as a chelator of mercury. The treatment itself made me quite ill, but within a couple of weeks of stopping I began activities - small weights, learn guitar, fix up things around the house etc. These are things I hadn't done for 15 years. My bedtime was reduced dramatically. This lasted for 9 months until I had a crash. I was debating whether to resume the chelation treatment as I had doubts about the doctor's diagnosis of mercury poisoning and was uncertain whether the chelation was the cause of the partial recovery.

    ALA is a relatively cheap treatment with relatively fewer side-effects and might be worth trying before spending up big on antiretrovirals.
  3. August59

    August59 Daughters High School Graduation

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    Has anyone used a good quality sustained-released version of ALA. Doesn't Cutlers protocol call for pretty substancial dose at 3-4 hour intervals? Also, goes back to discussion on another forum about it not completely chelating the metals\toxins completely out of the body because it has such a short half-life? I agree that it definitely is something to try given the benefits as opposed to any side effects. It's on my list to order and is why the initial question about quality sustained-release, controlled release, timed release as I'm under the assumption that they are all the same?
  4. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi August. I have been lurking at these forums for some time and have noted every new development with rising excitement. I believe this post about chelators is very important and perhaps has slipped under the guard of many visitors.

    There are quite a few differing views on where the ALA chelation process could break down - due to lack of research, as there are for other chelators. Cutler pushes ALA because it is one of the few chelators to get past the so called Blood Brain Barrier.

    I have not heard of sustained release ALA. I use Healthy Origins, Alpha Lipoic Acid, 100 mg, 120 Capsules from iHerb (hope this is ok, no connection to product). If product edited out, you can email me. I know that if I did not take next dose within half hour of 3-4 period, I got severe, painful headaches. Each night I just set my mobile alarm - it didn't disrupt my sleep much more than normal. Had pills beside the bed. Don't even think I fully woke. Dosage can be adjusted. Lower dosage, less side-effects. Cutler has dosage based on weight. Diminished returns from increasing dose. From my experiences I suggest start off low.
  5. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    August. I just realised I didn't fully address your point about the effectiveness of ALA as a chelator. As I understand it the above comment is a non-issue. As the first dosage begins to lose its potency and starts redepositing metals, the new dosage picks it up. Theoretically there should be no redepositing if you stick to the program. If you don't follow the program, you get the headaches - very timely reminders (to take next dose, and that the process might actually be working).
  6. natasa778

    natasa778 Senior Member

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    Thanks Rusty, very interesting re headaches esp that they would start so promptly after 4 hours. I had severe sudden headache after a few weeks of NAC, and later the same with olive leaf extract (chelating??). Have you tried any other chelators in the past? I think one of the main reasons AC 'pushes' ALA is that it is easy to dose around the clock. I know DMSA is also recommended by him, if it can be taken in the same way alongside ALA, and DMPS is approved if dosed every 8 hours...

    Do prescription antiretrovirals have to be taken around the clock in regular intervals?

    Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication.
    Alpha-lipoic acid, a naturally occurring disulfide-compound that acts as a cellular coenzyme, inhibits replication of HIV-1 in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with HTLV IIIB and HIV-1 Wal (a wild type HIV-1 isolate). We observed a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic effect) formation, reverse transcriptase activity and plaque formation on CD4-transformed HeLa-cells. An over 90% reduction of reverse transcriptase activity could be achieved with 70 micrograms alpha-lipoic acid/ml, a complete reduction of plaque-forming units at concentrations of greater than or equal to 35 micrograms alpha-lipoic acid/ml. An augmentation of the antiviral activity was seen by combination of zidovudine and low dose of alpha-lipoic acid (7 micrograms/ml). Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mono-nuclear cells and T-cell lines even in concentrations of greater than or equal to 70 micrograms/ml. Therefore, we propose the inclusion of alpha-lipoic acid into chemotherapy trials in combination with zidovudine. Baur A, et al Institut fr Klinische und Molekulare Virologie der Universitt Erlangen-Nrnberg. Klin Wochenschr. 1991 Oct 2;69(15):722-4.
  7. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Natasa. Perhaps thread should be retitled New. Inexpensive, safer alternative to XMRV antiretroviral treatment, to underscore its importance.

    I have not tried other chelators. Used ALA because it was accessible, cheap, could be used without medical supervision - seemed less problematic than others (DMSA, DMPS). I have tried many other so-called remedies, including olive leaf extract without any benefit.

    I am glad you posted Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication as I am making heavy weather of interpreting earlier chelation studies you posted earlier, and was starting to think I was going down the wrong track (brain fog). What is signficant is that ALA could work as relatively low dosages, when compared to other chelators mentioned.

    Cutler was adamant that ALA be taken every 3-4 hours because of its short half-life. I don't think this is really an issue with antibiotics - they work differently. Someone with more knowledge could perhaps explain better.

    As I inferred earlier, I was mistrustful of my doctor's diagnosis of mercury poisoning as he was making an assumption which didn't seem to have much science behind it, that I could find. The chelator connection with HIV and other viruses finding is beyond serendipity and I will be going back on ALA in the next few days. This study may have more relevance than any other posted over the last few months - big call, I know.
  8. caledonia

    caledonia

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    Very interesting, but I was on chelators for 6 months and nothing happened except my mercury levels got lower and my thyroid labs looked a lot better. Not that those aren't significant, but I didn't have any increase in functioning. On the other hand, the dose that I was on was much smaller than a normal person's dose, and I'm still not convinced that I have XMRV.
  9. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Calendonia. Just reading between the lines of the papers posted in this thread, the XMRV disintegration effect observed with ALA may have nothing to do with mercury levels - just a lucky coincidence. Regardless, there has always been some research showing a link between heavy metals and viruses. Cutler himself says that by reducing mercury you allow the immune system to fight the entero viruses.

    It seems that most of the chelators mentioned above required heavy dosages for anti(retro)viral effect. It seems that ALA does not. While the low dosage chelator you were taking may have been effective at removing mercury there is no evidence yet that lowering mercury in itself has an effect on xmrv levels. Also I am not convinced that the science behind measuring chronic mercury poisoning is watertight as yet. There is no blood test for chronic mercury. You may still have high chronic levels of mercury but are expressing less, or are showing higher expressions of mercury through urine or in hair (science shakey) as a result of improved delivery systems through liver, gall bladder etc. Some chelators work to improve delivery systems from the body, others are better at picking it up. Cutler likes ALA because it does both reasonable well, but neither as well as some of the others.
  10. natasa778

    natasa778 Senior Member

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    Yes and it is not just through "enabling" the immune system, actually much of it nothing to do with the immune system - are you aware of the work by the Swedish and Danish teams on this?

    There are too many to post here but if interested the easiest way to find them would be to in: Ilback, virus, metal, or something similar in Pubmed search engine (Ilback is the lead researcher of the Swedish team). Then some very interesting studies like "Tissue uptake of mercury is changed during the course of a common viral infection in mice." and "Virus induces metal-binding proteins and changed trace element balance in the brain during the course of a common human infection (coxsackievirus B3) in mice." will come up... Amazing stuff.
  11. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    No I wasn't. Sloppy thinking. ME-affected.

    As you say, these studies show viruses altering tissue uptake of mercury, rather than mercury impairing the immune system. A case of which came first chicken or the egg? Cut the viral (or bacterial) load and you reduce uptake, but perhaps still need to dig out mercury already locked up.

    I am embarrassed (but very grateful) at how easily you have come up with these studies. Thank you. I will endeavour to read them all, a bit at a time. I have also placed an online order for ALA.
  12. Sing

    Sing Senior Member

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    This is very hopeful news! Would you say more about, or link to, the Cutler protocol?

    Are there other doctors/health practitioners who use this treatment of ALA?

    Thank you!

    Sing
  13. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Sing, sorry to take so long to respond. Different time zone - had to sleep. Most of this information about chelators is quite old and perhaps out of fashion. Also regarded as alternative medicine. Everyone is into antiretrovirals at the moment. However I think it is worth a try. Also worth following the research trail.

    Cutler Protocol info: http://home.earthlink.net/~moriam/

    Cutler Protocol forum: http://curezone.com/forums/f.asp?f=638
  14. Adster

    Adster Senior Member

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    I just found this very interesting thread. Thanks to the OP for posting it. DMSA on the cutler protocol has been one treatment that has really helped me. A hair test has shown double normal range for mercury, but I wouldn't be surprised if this antiviral property of the drug is having an influence. Thought I'd revive it so others might read it.

    (Interestingly I got here by searching for HeLa, I'm reading about Henrietta Lacks right now. Fascinating and scary stuff)
  15. Chris

    Chris Senior Member

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    Hi; AOR make a "sustained release" form of (R) ALA that is claimed to release over 8-10 hours, so that 2-3 per day would cover the 24 hour cycle. I have been taking it for a while, with no special effects that I can attribute to it-am also taking AHCC. Was better for a while, but down again now.... Their website is www.aor.ca . Best, Chris

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