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Enteroviruses - revisted

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by globalpilot, Feb 3, 2012.

  1. globalpilot

    globalpilot Senior Member

    I thought I'd start a thread where we could share research on enteroviruses. Several of us, including myself, have been found to have excessive amounts of dsRNA in our gut biopsies by Dr. Chia.

    Here is a start:

    Molecular Mechanisms of Coxsackievirus Persistence in Chronic Inflammatory Myopathy: Viral RNA Persists through Formation of a Double-Stranded Complex without Associated Genomic Mutations or Evolution

    - this study looks at myopathy but does reference CFS. It explains how coxsackie may persist (in a dsRNA form)

    "The mechanism of enterovirus replication is not completely understood, but it is possible that downregulation of RNA polymerase activity occurs in damaged myofibers through changes in cellular proteins that participate as elements of the viral replication complex, resulting in production of double-stranded persistent RNA. As a potent inducer of interferon and other cell mediators, double-stranded RNA may itself be pathogenic (25). Activation of interferon-inducible protein kinase has multiple effects on cellular proteins, which, in addition to inhibiting viral replication, include upregulating the transcription of cytokine genes through activation of NF?B. In virus-induced myopathies, tissue injury could result directly from inducible nitric oxide synthase produced by muscle or through production of cytokines and other mediators such as those that have been implicated in the pathogenesis of fatigue syndromes (20). Equivalent levels of plus and minus strands of enterovirus RNA have been observed in patients with chronic fatigue syndrome (15), and what we have found in mouse muscle may now provide a basis for understanding the processes which are at work in human diseases (33). Whether pathogenicity in CIM is derived directly from the presence of viral RNA or requires some degree of translation is not known. The lack of deleterious mutations and the fact that all regions of the viral genome were amplified leaves open the possibility that under appropriate but as yet unknown conditions, persistent coxsackievirus RNA possesses the capacity to produce viral proteins or infectious virus, thereby promoting an ongoing immunopathic response in muscle. "
    Sidereal, Radio, SOC and 3 others like this.
  2. Waverunner

    Waverunner Senior Member

    This thread is a very good idea. I'm very interested in the implication of enteroviruses in ME/CFS.
  3. Timaca

    Timaca Senior Member

    Coxsackie B is part of my problem. My oxymatrine journey can be found here: http://hhv6foundation.proboards.com/index.cgi?board=antiviral&action=display&thread=200 In a nutshell it appears (by antibody titers) that I am battling various pathogens (HHV-6, EBV, Coxsackie B, Cpn and HSV1). In June of 2009, Coxsackie B4 was as high as the lab measures at ARUP lab (>=1:640) and B3 was quite high too 1:320. Oxymatrine brought those titers down (B4 to 1:40 and B3 to <1:10), and I felt better (not well but better). In April 2010, I got quite ill, and my WBC and platelets dropped well below the reference range. The doctors ran some labs on me and found that The Coxsackie B3 and B4 had jumped back to >=1:640 and 1:320. (In 3 weeks time they jumped from as low as they had ever been to that high again.) So we know my problem was Coxsackie related. B3 is now 1:80 and B4 1:160 so they are dropping again. And my Cpn IgA is dropping too due to the antibiotics I'm on. But, HSV 1 IgG is as high as the lab measures and IgM is "detected" sometimes also giving a low titer. So, in me, it's not just one pathogen causing me problems (apparently).

    For more info on Coxsackie B and enteroviruses see: http://chronicfatigue.stanford.edu/infections/entero.html

    Best, Timaca
  4. globalpilot

    globalpilot Senior Member

    I wonder why one person with enterovirus (yourself) would show high antibodies to various pathogens and another (myself) doens't show high antibodies. I didn't even show high antibodies to coxsackie. maybe we have different immune system abnormalities. I think, in myself, this infection may have become established when I was very young (not breastfed which confers IgA immunity against enteroviruses and lots of time at a lake).

  5. globalpilot

    globalpilot Senior Member

    Here is another one showing enteroviruses have antiapoptotic features:

    Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral Security Protein?

    - Since then, a wealth of data has been accumulated that shows that the activation of apoptotic pathways is a widespread, though not universal, response to picornavirus infection. Thus, apoptosis-inducing capacity was reported for coxsackieviruses B3, B4, and B5 (22, 54, 82), enteroviruses 70 and 71 (25, 27, 60, 88), human rhinoviruses 1B, 9, 14, and 16 (32, 92, 100), foot-and-mouth disease virus (53, 76), avian encephalomyelitis virus (62, 63), and hepatitis A virus (16, 43) and was the subject of several recent reviews (15, 102). The antiapoptotic activity of picornaviruses was studied predominantly by using poliovirus (3, 8, 13, 72) and coxsackievirus B3 (21, 36, 85).
    - 2A protease proteins of enterovirus and rhinovirus (unrelated to 2A proteins of cardioviruses), though apparently essential (70), also perform a set of anti-defensive functions very similar to those exhibited by L proteins of cardioviruses and aphthoviruses, namely the inhibition of host translation (59), the disruption of controllable nucleocytoplasmic traffic (12, 75), the suppression of interferon action (71), and others (56).
  6. globalpilot

    globalpilot Senior Member

  7. globalpilot

    globalpilot Senior Member

    Here is a study showing how the body deals with dsRNA in pancreatic beta cells. I don't know if the same would apply to the gut where Dr Chia is finding enterovirus dsRNA. But, it seems there is a specific mechanism for apoptosis of these cells and for those with persistent dsRNA this procedure must not be working properly. I wonder if the virus downregulates this procedure. If so, stopping viral translation should stop this problem. Maybe the emblica root can accomplish this.

    Exposure to the Viral By-Product dsRNA or Coxsackievirus B5 Triggers Pancreatic Beta Cell Apoptosis via a Bim / Mcl-1 Imbalance
    - We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA) and a diabetogenic enterovirus (Coxsackievirus B5). Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR) promotes eIF2? phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis.
  8. Hip

    Hip Senior Member

    Antivirals for Enteroviruses: Coxsackievirus B and Echovirus

    Here is a list of supplements and drugs that are antiviral for coxsackievirus B and echovirus, two enteroviruses strongly associated with ME/CFS. 1 2 3 4

    Antiviral Drugs for Coxsackievirus B:

    ribavirin (antiviral drug) 1
    arbidol (antiviral drug) 1
    amiloride (diuretic drug) 1
    fluoxetine (antidepressant drug) 1
    valsartan (ARB blood pressure drug) 1
    olmesartan (ARB blood pressure drug) 1
    lovastatin (statin drug) 1
    mycophenolate (immunosuppressive drug) 1

    Antiviral Drugs for Echovirus:

    ribavirin (antiviral drug) 1
    amantadine (antiviral drug) 1

    Antiviral Supplements for Coxsackievirus B:

    Terminalia chebula (haritaki, He Zi) antiviral for CVB3 and CVB5 1
    Emblica officinalis (Phyllanthus emblica, amla) root antiviral for CVB3 1 2
    Trichosanthes root (Tian Hua Fen) antiviral for CVB3 1
    Rhodiola rosea (golden root) antiviral for CVB3 1
    curcumin potently antiviral for CVB3 1
    emodin (from Japanese knotweed) antiviral for CVB3 and CVB4 1 2
    Astragalus membranaceus antiviral for CVB3 1
    Spatholobus suberectus Dunn (Ji Xue Teng) antiviral for CVB3 1 2
    ursolic acid antiviral for CVB1 1
    Bupleurum kaoi (Chai Hu) antiviral for CVB1 1
    Glycine max (black soybean extract, Dan Dou Chi) antiviral for CVB1 1
    DHEA (dehydroepiandrosterone) antiviral for CVB4 1
    sodium selenite (a form of selenium) antiviral for CVB5 1
    Epimedium (horny goat weed) antiviral for CVB4 and CVB5 1 2
    baicalein (found in Scutellaria baicalensis, Chinese Skullcap) antiviral for CVB3 1
    acemannan (aloe polymannose from aloe vera leaves) antiviral for CVB3 1
    Aegle marmelos Corr (bael fruit powder, bilva powder) antiviral for CVB1 to B6 1
    Azadirachta indica (neem leaf) antiviral for CVB1 to B6 1
    Sophora flavescens root (Ku Shen) antiviral for CVB3 1 2
    oxymatrine (from Sophora flavescens root) immunomodulator for coxsackievirus B 1
    Isatis tinctoria (dyer’s woad, Da Qing Ye, Ban Lan Gen) antiviral for CVB3 1
    shuang huang lian (Chinese herbal formula) antiviral for CVB3 1
    yakammaoto (Chinese herbal formula) antiviral for CVB4 1
    cinnamaldehyde (cinnamon essential oil is about 90% cinnamaldehyde) antiviral for CVB3 1
    hyaluronic acid antiviral for CVB5 1
    simalikalactone D (from Quassia amara) antiviral for coxsackievirus 1
    Rheum palmatum root (Chinese rhubarb, Turkish rhubarb) antiviral for CVB3 1
    raoulic acid (from Raoulia australis) antiviral for CVB3 1
    fatty acid synthase inhibitors (amentoflavone, oleic acid, keemun tea, Parasitic loranthus, EGCG) antiviral for CVB3 1 2
    selenium deficiency increases virulence of CVB3 1
    vitamin E deficiency increases virulence of CVB3 1
    copper deficiency increases virulence of CVB3 1

    Antiviral Supplements for Echovirus:

    Betulin (from birch bark) antiviral for EV6 1
    Spatholobus suberectus Dunn (Ji Xue Teng) antiviral for EV9 and EV29 1
    shuang huang lian (Chinese herbal formula) antiviral for EV11 1
    garlic antiviral for EV11 1
    latex from fig fruit (Ficus carica) antiviral for EV11 1
    beta-lapachone (from Lapacho) antiviral for EV19 1

    Antivirals for Enteroviruses and Picornaviruses in General:

    itraconazole (anti-fungal) antiviral for enteroviruses 1
    nicotinamide (aka niacinamide, vitamin B3) antiviral for enteroviruses 1
    EGCG (extract from green tea) antiviral for enteroviruses 1
    hinokitiol (found in hiba oil) antiviral for picornaviruses 1
    guanidine potent but toxic antiviral for picornaviruses 1 2 3

    My Experiences With These Antivirals:

    I have tried nearly all of these antiviral supplements and drugs, often taking up to a dozen of these simultaneously as an antiviral cocktail. Although I noted some improvements in my ME/CFS symptoms when taking these anti-enteroviral cocktails, I did not notice any significant benefits (although I only tested these supplements for a month or so, and have not tried them for a longer term test; ideally they should be tested for around 3 to 6 months in order to properly gauge their effectiveness).

    Antiviral Effects:

    From the studies referenced above, the following info was extracted:

    • Spatholobus suberectus extracts have remarkable anti-CVB3 activity in vitro. CVB3 messenger RNA (mRNA) is significantly inhibited by Spatholobus suberectus.
    • Amiloride strongly inhibits the RNA replication of CVB3.
    • Curcumin potently inhibits coxsackievirus replication through dysregulation of the ubiquitin-proteasome system (UPS).
    • Trichosanthes kirilowii (the ethyl acetate extract) has a significant protective effect on HeLa cells infected with CVB3 (an in vitro study).
    • Aegle marmelos Corr (bael fruit powder, bilva powder) has similar efficacy to ribavirin. Marmelide, from Aegle marmelos Corr, interfered with early events of the replicative cycle like adsorption and penetration.

    Non-Cytopathic Enteroviruses: the Intracellular Side of an Enterovirus Infection:

    It is thought that an unusual infectious entity called a non-cytopathic enterovirus may be a major problem in ME/CFS. 1

    Enteroviruses initially infect the human body as a regular virus that you catch. However, when such an enterovirus infection turns into a chronic condition, this regular enterovirus can alter its form within your body, and change into a different infectious entity called a non-cytopathic enterovirus. When this happens, you effectively have two different infections going on in your body simultaneously: one infection with regular enteroviruses, and another second infection with non-cytopathic enteroviruses. Whereas regular enteroviruses mainly live outside of our cells, by contrast, non-cytopathic enteroviruses permanently reside inside human cells, as an intracellular infection.

    Non-cytopathic enterovirus infections within cells are composed of naked single and double stranded RNA (ssRNA and dsRNA) deriving from the regular enterovirus genome that live inside human cells as an intracellular infection. However, it is thought that the permanent presence of non-cytopathic enteroviruses within human cells may be disruptive to cellular metabolism, and these non-cytopathic enteroviruses may play a major role in ME/CFS.

    I am not sure if any of these antivirals will have any effect against these non-cytopathic enteroviruses, though amiloride inhibits the RNA replication of coxsackievirus B inside human cells, and Spatholobus suberectus inhibits coxsackievirus B messenger RNA (mRNA).

    Dr John Chia has mentioned1 that a new hepatitis C drug under development may be able to kill the non-cytopathic enterovirus intracellular RNA infection that is likely causing havoc in ME/CFS.

    Non-cytopathic enteroviruses are also known as: non-cytolytic enteroviruses, terminally-deleted enteroviruses and defective enteroviruses.

    General Notes:

    • The anti-enteroviral compound in Emblica officinalis (amla) is called phyllaemblicin B.
    • The anti-enteroviral compound in Rhodiola rosea is called salidroside.
    • The anti-enteroviral compound in Epimedium (horny goat weed) is called icariin.
    • The anti-enteroviral compound in Sophora flavescens root (Ku Shen) is called sophoridine. (Sophora flavescens root also contains oxymatrine and matrine).
    • The anti-enteroviral compound in Aegle marmelos Corr is called marmelide. Maximum safe daily dose of Aegle marmelos Corr (bael fruit powder, bilva powder) is 40 grams (by my calculations, based on data from the Aegle marmelos study).
    • EGCG inhibits folate.
    • Emodin is a laxative.
    • Amiloride should not be taken with lithium or spironolactone.
    • Trichosanthes root is toxic in higher amounts.
    • Sodium selenite (a form of selenium) is not to be confused with sodium selenATE (another form of selenium).
    • The Chinese herbal formula Qi Hong = Astragalus membranaceus + Rhodiola rosea + Sophora flavescens.
    • The Chinese herbal formula Shuang Huang Lian = Lonicera Japonica + Scutellaria baicalensis + Fructus Forsythiae + Saccharum.
    • Isatis tinctoria is sometimes also called Isatis indigotica.

    Antivirals Able to Cross the Blood-Brain Barrier

    Since ME/CFS may involve an enteroviral infection within the central nervous system, anti-enteroviral compounds that can penetrate the blood-brain barrier might be of particular benefit. I found studies showing that the following antiviral compounds can cross the blood-brain barrier:

    • Icariin from Epimedium (horny goat weed) might cross the blood-brain barrier into brain tissues. 1
    • Baicalein from Chinese Skullcap is able to penetrate the blood-brain barrier. 1
    • Indirubin from Isatis tinctoria herb (Da Qing Ye), and from Indigo naturalis powder (Qing Dai), is able to cross the blood-brain barrier. 1

    Some Sources for These Supplements:

    • Glycine max (black soybean extract, Dan Dou Chi): bristolbotanicals.co.uk.
    • Spatholobus suberectus (Ji Xue Teng): ktbotanicals.com, bristolbotanicals.co.uk.
    • Aegle marmelos Corr (bael fruit powder, bilva powder): garrysun.com, bilva.in, ayurvedicdietsolutions.com, ayurveda.com, ayurveda-market.com.
    • Ursolic acid: the body-bulding supplement E-Pharm Ursobolic® contains 50 mg of ursolic acid per capsule. The peel of an apple apparently contains around 50 of ursolic acid.

    Anti-Enteroviral Drugs in the Research Pipeline:

    The following pharmaceuticals have shown anti-enterovirus or anti-picornavirus activity, and are currently under research, but are not as yet generally available.

    BTA-798 (vapendavir)
    TTP 8307
    SCH 48973
    Ro 09-0179
    SDZ 35-682
    Picovir (pleconaril)
    R77975 (pirodavir)
    LY-122772 (enviroxime)
    WIN 51711 (disoxaril)
    WIN 54954
    T-705 (favipiravir, Avigan)
    Last edited: Oct 19, 2015
    paolo, Sidereal, Helen and 8 others like this.
  9. fairlight


    global-thank you for starting this thread and the great info posted. I am also a patient of Dr. Chiia's and have high levels of enteroviruses shown on biopsies of the gut.

    Hip-thank you for the great info you've posted. Do you know why the diuretic drug amilorid is used against enteroviruses? Thanks.

    The hep c drug will cost $60,000. :-(
  10. Enid

    Enid Senior Member

    Thanks to you all for this very interesting and informative thread. Never doubted the enteroviral origins (but which) in my case.
  11. Hip

    Hip Senior Member

    Hi Fairlight

    Wow, $60,000 seems a lot for this new hep C drug though if this new drug completely cures ME/CFS, it puts this in a different perspective. I believe Dr Chia thinks it may eradicate the enterovirus infection from our cells, thus possibly leading to a cure.

    Do you know the name of this new hep C drug, by the way? I am trying to find more information about this new drug, to read up on it. Perhaps you could ask Dr Chia the name of it when yo next see him? I am not sure why this new hep C drug is not getting more attention, given it has a theoretical possibility of curing ME/CFS.

    I don't think amiloride is generally prescribed to fight enteroviruses, but a study I uncovered said that it does have an anti-enterovirus effect. I did try amiloride, but without much success though it did reduce my anxiety levels noticeably, for some unknown reason.
  12. Jenny

    Jenny Senior Member

    Hi Hip

    Ribavarin isn't particularly new - it's been used to treat Hep C for many years. A newer drug is telaprevir which is now used in combination with ribavarin and pegalated interferon.

    My husband started treatment for his Hep C with this combination 2 weeks ago - he's on a trial to see whether people who've had a liver transplant (and therefore on immune suppresant drugs) benefit from it. He's been given around a 50% chance of success given that earlier treatment with interferon and ribavarin failed many years ago, and that his liver is now being attacked again, 4 years after transplant.

    He's feeling very ill on the treatment - but can still do much more than me!

    The trial will continue for nearly a year if he does OK. I've no idea how much these drugs cost, but I'm amazed at the resources being put into this trial. He has blood tests 2 or 3 times a week, monitoring of heart, kidneys etc, regular pep talks over the phone from docs.

    If only...............
  13. Hip

    Hip Senior Member

    No, it is not ribavirin I am referring to. I am talking about a newly-developed hep C drug, that I believe is still in clinical trials, and not on the market yet.

    Dr Chia thinks this new hep C drug may eradicate the enterovirus infection from within our cells, possibly leading to a cure of ME/CFS.

    I would just like to know the name of this new hep C drug (or its code number, if it has not got a name yet).
  14. Jenny

    Jenny Senior Member

    OK. There are over 60 Hep C drugs in various stages of development.
  15. Hip

    Hip Senior Member

    Hopefully Fairlight will know the name of this new hep C drug.

    As you say, there are many new hepatitis C drugs under development (this web page lists them).
  16. CBS

    CBS Senior Member

    Was it DRACO? Dr. Chia has discussed this as a potential treatment for enteroviruses that could be available in 4-6 years. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022572
  17. Hip

    Hip Senior Member

    I don't think it was DRACO, which is only in the early stages of research, and which is also a broad spectrum antiviral. What I read in this article here is that it was specifically a hepatitis C drug under development that will be able to wipe out the enterovirus RNA inside human cells.
    Last edited: Feb 19, 2015
  18. FunkOdyssey

    FunkOdyssey Senior Member

    Has anyone tried higher doses of sodium selenite (400-600 mcg daily) for extended lengths of time (6+ months)? Selenium status seems to determine vulnerability to a wide range of viruses, and this particular form of selenium, sodium selenite, shuts down coxsackievirus B replication impressively well. Check out Keshan disease, where CVB3 causes myocarditis and sodium selenite treats it handily.

    Also there is the possibility that coxsackievirus actively depletes host stores of selenium to favor its persistence: http://www.ncbi.nlm.nih.gov/pubmed/17590522

  19. Hip

    Hip Senior Member

    I have taken 400 mcg of selenium daily on an empty stomach for a good two years now, as a general antiviral. I currently take the selenomethionine form of selenium, but I have also tried the sodium selenate and sodium selenite forms too.

    As you say, the sodium selenite form of selenium has good antiviral effects against coxsackievirus B:
    Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease

    Note: this study says zinc counteracts the antiviral effect of selenite (zinc inhibits the toxicity of selenite, and the antiviral effects of selenite derive from its toxicity).

    And selenium deficiency is linked to increased virulence of coxsackievirus B: see these studies:
    Increased virulence of a human enterovirus (coxsackievirus B3) in selenium-deficient mice.
    Selenium and viral virulence.

    So I keep taking selenium to help fight coxsackievirus B.

    I have also tried taking high doses of sodium selenite, up to 1,600 mcg daily. Unfortunately, this dosage had the side effect of creating significant irritability, so I had to discontinue. Though if I can find a workaround for this irritability side effect, I would try this high dose of sodium selenite again.

    Generally, the recommended safe maximum daily amount of selenium is 800 mcg. However, people taking sodium selenite as an anti-cancer agent take up to 6,000 mcg daily(!), and seem to have no problems even after years on this super high dosage. Many studies show sodium selenite has potent effects specifically against chemotherapy-resistant cancers, and I know someone who had a chemotherapy-resistant cancer that doctors said would kill him in a matter of months, but he is still alive and well years later from daily super high dose of sodium selenite.

    Note that my ME/CFS has improved quite a bit over the last two years. Two years ago, I would often get a couple of days a week in which I was so tired I'd sleep all night, and then sleep most of the day too; but now I almost never sleep during the day — though I still need 10 to 12 hours sleep at night.

    In terms of the supplements likely responsible for this increased health: the only supplement that I have taken consistently almost every day for the last two years of improving health is selenomethionine 400 mcg daily. I have also taken N-acetylglucosamine (NAG) 750 mg consistently each day for the last year, and I believe NAG has been extremely helpful for my ME/CFS, and particularly for my anxiety symptoms (I wax lyrical about NAG on this thread). I have also taken horsetail herb (silica) daily for the last 18 months to control my recurrent kidney infection.
    Adlyfrost and FunkOdyssey like this.
  20. Charles555nc

    Charles555nc Senior Member

    Do you think that taking sodium selenite in the morning and then antioxidants at night (so as not to detoxiify the anti viral effects) would be a good game plan?

    I tested positive for coxsackie B virus.

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