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Enteroviruses - revisted

Hip

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Have you evrr heard of Dr Chia or any association of Echovirus type 30 with cfs? Only 1:320
You have titers of 1:320 for echovirus 30 in the ARUP Lab tests? I believe Dr Chia would consider that evidence of a chronic active enterovirus infection. Dr Chia says the coxsackievirus B and echovirus serotypes that most commonly cause ME/CFS are:
  • CVB3 and CVB4 first and foremost
  • Then CVB2, EV6, EV7 and EV9
  • And then much less EV11
He does not mention EV30, but I would think it may be able to cause ME/CFS along with these other serotypes. So EC30 could be behind your ME/CFS.


Also had cvb2 and cvb4 @ 1:80 and 1:160 respectively.

Dr chia would not consider these last two to be of any significance woukd he?
Your CVB4 titers of 1:160 are one level below the threshold of 1:320 that Chia uses as the indication for active infection. But note that the test-retest accuracy of these types of antibody assays is often give or take one level. So for example, if you tested again the next day, you might find your CVB4 comes out as one level higher at 1:320, or equally one level lower at 1:80, just due to the inherent slight day to day inaccuracy of the antibody assay.

So you might want to focus on EV30, but remain suspicious of CVB4, especially as CVB4 seems to be one of the most common enteroviruses that Dr Chia finds active in his ME/CFS patients.


In any case, whether it is EV30 and/or CVB4 that night be behind your ME/CFS, the treatment Dr Chia uses for such enterovirus infections is oxymatrine. Sometimes he adds in another immunomodulator inosine. He also uses the antiviral Epivir against some enteroviruses, and more recently has been using tenofovir.
 
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halcyon

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Have you evrr heard of Dr Chia or any association of Echovirus type 30 with cfs? Only 1:320
1:320 is a significant titer for that serotype. Echovirus 30 is what triggered my illness. Mine fluctuates between 1:320 and 1:640. It’s not a serotype that Chia has seen a lot of in the past.
 

Hip

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By the way, for ME/CFS with active echovirus infection, my pharmacokinetic calculations indicated that betulinic acid (from Chaga mushroom supplement) has some useful antiviral effect for echovirus 6 (and possibly other echovirus types, though this is not proven, as the antiviral study focused on EV6).

In these pharmacokinetic calculations, I calculate what I call the Potency Factor for various antiviral drugs, supplements and compounds. The Potency Factor is a figure which represents the strength of the antiviral in vivo when taken by humans.

The Potency Factor for betulinic acid against EV6 came out as 176. To put this into context, the Potency Factor of the (unavailable) enterovirus antiviral pleconaril against EV11, EV24 and EV30 came out as 1,080. Generally speaking, the Potency Factor of most standard pharmaceutical drugs comes out in the thousands. For example, the Potency Factor of the powerful antiviral Valcyte against cytomegalovirus came out to be 4,410.

So betulinic acid's Potency Factor of 176 is only modest, but it is possible it might provide mild benefits to ME/CFS patients with active echovirus.


Betulinic acid is available as a supplement: some Chaga mushroom supplements contain up to 2% betulinic acid. See: 1 2 3 The Chaga mushroom dosage is around 500 mg twice daily (500 mg corresponds to 10 mg of betulinic acid).

If you double the dose you will double the Potency Factor; but you might want to be cautious about going above the maximum recommended dose of Chaga mushrooms (I am not sure what the max recommended dose is).

Betulinic acid itself appears to be fine at higher doses in mice: in various mice studies, betulinic acid doses of 20 to 250 mg/kg were used. This corresponds to human doses of 1.6 to 20 mg/kg, which for an 80 kg human, that is an oral dose of 128 to 400 mg of betulinic acid.


In vitro, betulinic acid is a very potent antiviral for echovirus, slightly better than pleconaril. However, betulinic acid has poor absorption characteristics in the gut, and thus low oral bioavailability.

I believe taking Chaga mushroom / betulinic acid with a fatty meal may improve absorption. This is because betulinic acid has very poor water solubility (which usually equates to low oral bioavailability), but dissolves to some extent in oil. Betulinic acid dissolves well in DMSO, so could be administered that way.

If you could increase the bioavailability by say 5 times using DMSO (to guess a figure off the top of my head), then this would correspondingly increase the antiviral Potency Factor by 5 times.
 
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flitza

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@Hip
I just had the entero test at arup labs done from Australia. So its still possible.

Have you evrr heard of Dr Chia or any association of Echovirus type 30 with cfs? Only 1:320

Also had cvb2 and cvb4 @ 1:80 and 1:160 respectively.

Dr chia would not consider these last two to be of any significance woukd he?
Yes. I see Dr. Chia and have an Echovirus that he feels is significant.
 

JES

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Stumbled on a website with some information about Enterovirus infections and possible antivirals. Some of the evidence seemed anecdotal and I don't know whether it would be of any use for non-acute enterovirus infection like the one present in CFS, but thought it would be of interest nevertheless.

Treatment of Coxsackieviruses
Thankfully, the overwhelming majority of coxsackieviral infections are mild. Complete recovery is the rule, and serious disease is rare. The severity and symptom patterns of these infections tend to cluster in local outbreaks. In Singapore, for example, coxsackievirus was found to be the cause in a group of SIDS cases (Annals of the Academy of Medicine of Singapore, Nov 1994). Frighteningly, medicine has had very limited success in treating coxsackieviral infections.

I do have a few suggestions (in addition to excellent supportive care, restriction of physical activities, and classical medications for heart failure) for the rare child who is seriously ill:

Acyclovir (Zovirax) is an antiviral medicine that has been used extensively in the treatment of herpes and chickenpox. Although according to our understanding it shouldn’t work against coxsackieviruses, it does seem to help. In one study, significant improvement occurred within 24 hours of initiating therapy, and symptoms were gone within 5 days (Cutis, April 1996).

Given this broader usefulness than expected of at least one antiviral medicine, I suspect that some of the drugs developed to fight the AIDS virus may also be of use against coxsackievirus.

In Sweden, an antiviral drug called WIN 54954 (also called 5-(5-(2.6-dichloro-4-(5.5-dihydro-2-oxazolyl)phenoxy)pentyl)-3-methyl-isoxaz ole) has been shown to be effective specifically against coxsackieviral myocarditis — in mice. In one study, mortality rates dropped from 100% to 15% if therapy was started within one day of the beginning of the illness (Scandinavian Journal of Infectious Diseases, 1993 Supplement). It was even more effective when combined with an immune stimulant called LS 2616. Researchers are now interested in studying these treatments in humans with coxsackieviral myocarditis.

Another approach that has already had some success in humans is to give intravenous immunoglobulin. This contains antibodies to coxsackieviruses made by people who have effectively fought off the infection. One child was apparently dying from coxsackieviral meningitis and encephalitis. The child had a dramatic and complete recovery when given IV immunoglobulin (Journal of Neurologic Sciences, April 1995).

Other immunosuppressive therapies such as azathioprine, prednisone, and cyclosporine have also been used to treat coxsackievirus, but they have not been rigorously studied through research trials, so their efficacy is unclear at this time (Am J Health Syst Pharm, January 2008).

Exciting work has also been done with a Chinese herb called Astrogalus membranaceous. This herbal therapy has been shown in several precise, sophisticated and convincing studies to be helpful in treating and preventing coxsackieviral heart disease (Chung Hsi I Chieh Ho Tsa Chih, May 1994, Nov 1994, and August 1995) (Chinese Medical Sciences Journal, Dec 1993 and Sep 1995).
 

perrier

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Not sure if this is to thread to post.

I'm still wondering what Dr. Davis thinks about Dr. Chia's thesis. Do we have any news? I ask because earlier in this thread it states that Dr. Davis didn't find active viral infection, and found more in the controls.

However, in Dr. Chia's tissue biopsies, there is evidence of enterovirus.But I don't know if Dr. Chia tested controls.

I'd dearly like to know what Dr. Davis thinks. Please update. Thanks.
 

Hip

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I'm still wondering what Dr. Davis thinks about Dr. Chia's thesis. Do we have any news? I ask because earlier in this thread it states that Dr. Davis didn't find active viral infection, and found more in the controls.
Do you mean Dr Ron Davis (there's also a Dr Mark Davis in ME/CFS research)? Would you have a link to an article about not finding active infection. A lot rests on how you test for infection, and how you interpret the results of the test.

A lot of ME/CFS patients have high IgG antibody titers to enterovirus and/or herpesvirus infections — high titers that you don't tend to find in the general population. Some doctors interpret those high titers as indicating a chronic active infection somewhere in the body; whereas others think the high titers might just be due to immune dysfunction. In the case of enterovirus, though, we know through tissue biopsies of ME/CFS patients that there is a chronic active intracellular infection in the tissues, so the high titers may be a result of this tissue infection.
 

perrier

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Do you mean Dr Ron Davis (there's also a Dr Mark Davis in ME/CFS research)? Would you have a link to an article about not finding active infection. A lot rests on how you test for infection, and how you interpret the results of the test.

A lot of ME/CFS patients have high IgG antibody titers to enterovirus and/or herpesvirus infections — high titers that you don't tend to find in the general population. Some doctors interpret those high titers as indicating a chronic active infection somewhere in the body; whereas others think the high titers might just be due to immune dysfunction. In the case of enterovirus, though, we know through tissue biopsies of ME/CFS patients that there is a chronic active intracellular infection in the tissues, so the high titers may be a result of this tissue infection.
Dear Hip,
I don't have a link; this morning, I recall reading here on a thread a short list of Dr Ron Davis' findings. And I noted that active viral infection was apparently not found, and the controls had more evidence of viral infection. ( I hope I am not garbling things here.)
I am really anxious to know what Dr. Ron Davis and his team think of the enterovirus issue. Our dearest family member tested positive for the stomach biopsy, for enterovirus.

Is this the cause of this horror illness, I don't know. But I do think that at this point this should be clarified. Is it or is it not enterovirus related. There should be some gathering of minds on this.

Young people are in horrific situations, in dark rooms, day after day, month after months, year after year.

So, I was just wanting to know if Dr. Ron Davis had examined Dr. Chia's thesis.
 

Hip

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But I do think that at this point this should be clarified. Is it or is it not enterovirus related. There should be some gathering of minds on this.
What you will find is that different researchers will have different views. Some favor the viral theory of ME/CFS, others think that some kind of immune dysfunction is the cause. And there are other theories too.

Because the evidence for all these theories is less than conclusive at this point in time, and because all these researchers are investigating their own angle on this disease, you won't get to get much gathering of minds — and maybe that is in some sense a good thing, in that if the problem is approached from various perspectives, we can hope that at least one of those approaches will bear fruit.

But I think a lot of patients feel that these various researchers should compare notes more often.

Perhaps eventually some of these approaches will merge together: for example, in future we might in find that immune dysfunction is indeed the cause of ME/CFS, but that ongoing viral infection exacerbates or maintains the immune dysfunction, thus connecting these different areas of research.

In terms of treatments for ME/CFS that are available today (that help a some patients), most of those are antiviral or immunomodulatory.
 

JES

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Dear Hip,
I don't have a link; this morning, I recall reading here on a thread a short list of Dr Ron Davis' findings. And I noted that active viral infection was apparently not found, and the controls had more evidence of viral infection. ( I hope I am not garbling things here.)
I am really anxious to know what Dr. Ron Davis and his team think of the enterovirus issue. Our dearest family member tested positive for the stomach biopsy, for enterovirus.
I reckon one problem was that Ron Davis only looked for viruses in the blood, and as you say, the way to optimally diagnose enterovirus infection would be through biopsy. The blood tests that exist for enterovirus infection are often inaccurate, which is why Chia uses a specific lab for testing. So IMO the lack of viruses found by Davis' methodology, I wouldn't count it as any kind of proof for enterovirus not being a factor in CFS. Hopefully with collaboration of Davis and Chia, we will finally get a definite answer on this soon.

I also have to mention that even if there is enterovirus infection confirmed by stomach biopsy, that alone doesn't confirm that CFS of your family member is driven by enterovirus. This because there is a percentage of healthy people that also harbour enteroviruses in their stomach.
 

perrier

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I reckon one problem was that Ron Davis only looked for viruses in the blood, and as you say, the way to optimally diagnose enterovirus infection would be through biopsy. The blood tests that exist for enterovirus infection are often inaccurate, which is why Chia uses a specific lab for testing. So IMO the lack of viruses found by Davis' methodology, I wouldn't count it as any kind of proof for enterovirus not being a factor in CFS. Hopefully with collaboration of Davis and Chia, we will finally get a definite answer on this soon.

I also have to mention that even if there is enterovirus infection confirmed by stomach biopsy, that alone doesn't confirm that CFS of your family member is driven by enterovirus. This because there is a percentage of healthy people that also harbour enteroviruses in their stomach.
Thanks Jes,
OK, I did not know that even healthy folks harbour enterovirus.
The blood test also came out positive for enterovirus. This was done when the CFS first hit, over night, as it were.
 
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List of 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 chronic fatigue syndrome / myalgic encephalomyelitis (ME/CFS).

Note though that antiviral effects in vitro (in cell line tests) may not necessarily translate to effects in vivo (in the body), when the drug or supplement is taken orally. This is because with in vitro studies, they use a certain concentration of the drug or supplement in a cell line to achieve an antiviral effect. But that concentration may be too high to achieve in the body when the drug or supplement is taken orally.

Dr John Chia has found that the enteroviruses most commonly found as active infections in ME/CFS patients are: 1
  • CVB3 and CVB4 first and foremost
  • Then less frequently CVB2, EV6, EV7 and EV9; and then much less frequently EV11


Antiviral Drugs for Coxsackievirus B:

interferon alpha (immunomodulatory drug) for CVB3 1
ribavirin (antiviral drug) antiviral for CVB3 1
OSW-1 (saponin) broad-spectrum antiviral for enteroviruses including CVB3, poliovirus, rhinovirus 1
umifenovir
(Arbidol, Russian antiviral drug) antiviral for CVB3, CVB5 1 2 and CVB4 1
fluoxetine (antidepressant drug) antiviral for CVB1, CVB2, CVB3 1 2 and CVB4 1
pirlindole
(Pyrazidol, MAO-A antidepressant) antiviral for CVB3, and antiviral for other CVBs and echoviruses 1
dipyridamole (vasodilator) broad-spectrum antiviral for picornaviruses including CVB3 1 2
itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including CVB3, CVA16, poliovirus, enterovirus-71, enterovirus 68, rhinovirus 1 2
bosentan
(pulmonary hypertension drug) antiviral for CVB3 (and likely all CVBs) 1 More info here.
valsartan (ARB blood pressure drug) antiviral for CVB3 (and likely all CVBs) 1 More info here.
olmesartan (ARB blood pressure drug) antiviral for CVB3 1
lovastatin (statin drug) antiviral for CVB3 1
mycophenolate (immunosuppressive drug) antiviral for CVB3 1
oseltamivir (Tamiflu, antiviral for influenzavirus) antiviral for CVB3 and CVB4 1 (see Table 1 in the raoulic acid full paper)
amiloride (diuretic drug) antiviral for CVB3 1 2 3 4
arsenic trioxide (leukemia drug) antiviral for CVB3 1 2
glyceryl trinitrate and isosorbide dinitrate antiviral for CVB3 1
gemcitabine (chemotherapy drug) antiviral for CVB3 and CVB3 replicons (non-cytolytic CVB3) 1


Note that Dr John Chia found that interferon and ribavirin are effective against CVB3 and CVB5 infections, but found these drugs were not effective against CVB4 infections. 1 2


Antiviral Drugs for Echovirus:

ribavirin (antiviral drug) antiviral for EV5, EV11 and EV18 1 2 3
amantadine (antiviral drug) antiviral for EV5 and EV18 1 2
fluoxetine (antidepressant drug) antiviral for EV1, EV9 and EV11 1
itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including EV11 1 2
dipyridamole
(vasodilator) broad-spectrum antiviral for picornaviruses 1 2
pirlindole (Pyrazidol, MAO-A antidepressant) antiviral for echoviruses 1


Antiviral Supplements for Coxsackievirus B:

dihydroquercetin (DHQ, a flavonoid) is a antiviral (as good as ribavirin) for CVB4. 1 Used by Dr Chia.
Aegle marmelos (bael fruit, bilva) antiviral (as good as ribavirin) for CVB1 to CVB6 1
Emblica officinalis (Phyllanthus emblica, amla) root antiviral for CVB3 1 2
shuang huang lian
(Chinese herbal formula) antiviral for CVB3 1 2
garlic antiviral for CVB3 1
curcumin antiviral for CVB3 1
chlorogenic acid
(6% in coffee; 50% in green coffee bean) antiviral for CVB3 and CVB5 1 2
baicalein (from Scutellaria baicalensis, Chinese skullcap) antiviral for CVB3 1
Paris polyphylla (Qi Ye Yi Zhi Hua, Chong Lou) antiviral for CVB3 and enterovirus 71 1
raoulic acid (from Raoulia australis) antiviral for CVB3 and CVB4 1
Dodonaea viscosa (hopbush) antiviral for CVB3 1
oroxylin A
(from Scutellaria baicalensis) may be antiviral for CVB3 1 and for enterovirus 71 1
oxymatrine
(from Sophora flavescens root) immunomodulator for coxsackievirus B 1
ursolic acid antiviral for CVB1 and enterovirus 71 1
apigenin
antiviral for CVB1 and enterovirus 71 1
emodin
(from Japanese knotweed, aloe vera, rhubarb) antiviral for CVB3, CVB4 and CVB5 1 2 3
Spatholobus suberectus
(Ji Xue Teng) antiviral for CVB3 and CVB5 1 2 3 4
Sophora tonkinensis
(Shan Dou Gen) antiviral for CVB3 and CVB5 1
Terminalia chebula (haritaki, He Zi) antiviral for CVB3 and CVB5 1
Trichosanthes root (Tian Hua Fen, Chinese cucumber) antiviral for CVB3 1
Rhodiola rosea (golden root) antiviral for CVB3 1
Astragalus membranaceus antiviral for CVB3 1
Bupleurum (Chai Hu) antiviral for CVB1 1
Glycine max (black soybean extract, Dan Dou Chi) antiviral for CVB1 1
DHEA (dehydroepiandrosterone) protective during CVB4 infection 1
5-androstenediol 100 times more protective than DHEA during CVB4 infection 1 2 (more info)
sodium selenite (a form of selenium) antiviral for CVB5 1
Epimedium (horny goat weed) antiviral for CVB4 and CVB5 1 2 3
acemannan
(aloe polymannose from aloe vera leaves) antiviral for CVB3 1
Azadirachta indica (neem leaf) antiviral for CVB1 to CVB6 (but most effective for CVB4) 1
sophoridine (from Sophora flavescens root, Ku Shen) antiviral for CVB3 1 2
oxymatrine (from Sophora flavescens root, Ku Shen) antiviral for CVB3 and immunomodulator for coxsackievirus B 1 2
Isatis tinctoria (dyer’s woad, Da Qing Ye, Ban Lan Gen) antiviral for CVB3 1
Indirubin derivative E804
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
Quassia amara antiviral for CVB2 1
Rheum palmatum root (Chinese rhubarb, Turkish rhubarb) antiviral for CVB3 1
fatty acid synthase inhibitors (these include: amentoflavone, oleic acid, keemun tea, Parasitic loranthus, EGCG) are antiviral for CVB3 1 2
EGCG
(from green tea) antiviral for CVB3 1
clinoptilolite (a natural zeolite) antiviral for CVB5 1
selenium deficiency increases virulence of CVB3 1
vitamin E deficiency increases virulence of CVB3 1
copper deficiency increases virulence of CVB3 1
nicotinamide (aka: niacinamide, vitamin B3) antiviral for CVB4 and CVB5 1
ginsenosides antiviral for CVB3 1
wild berry fruit extracts antiviral for CVB1 1
berberine antiviral for CVB3 1
chrysin antiviral for CVB3 1
Re Du Ning antiviral for CVB3 1
Spirulina platensis antiviral for CVB4 1
Houttuynia cordata antiviral for CVB3 and CVB6 1
fucoidan antiviral for CVB4 1


Antiviral Supplements for Echovirus:

shuang huang lian (Chinese herbal formula) antiviral for EV11 1
garlic antiviral for EV11 1
oxymatrine (from Sophora flavescens root) immunomodulator for echovirus 1
betulin and betulinic acid (from birch bark and Chaga mushroom) antiviral for EV6 1
Spatholobus suberectus Dunn (Ji Xue Teng) antiviral for EV9 and EV29 1 2
Sophora tonkinensis
(Shan Dou Gen) antiviral for EV9 and EV29 1
latex from fig fruit (Ficus carica) antiviral for EV11 1
beta-lapachone (from Lapacho) antiviral for EV19 1
clinoptilolite (a natural zeolite) antiviral for EV7 1
lactoferrin antiviral for EV5 1
bismuth salts (such as bismuth subsalicylate) antiviral for EV12 1
Re Du Ning antiviral for EV11 1
serum albumin (of bovine and human origin) antiviral for EV7 and other echoviruses 1
EGCG (from green tea) antiviral for EV11 1


Antivirals for Enteroviruses and Picornaviruses in General:

lamivudine (Epivir) an antiviral used by Dr Chia for enterovirus infections, although he found Epivir is not effective for EV6 and EV7. 1
EGCG (extract from green tea) antiviral for enteroviruses 1
hinokitiol (found in hiba wood essential oil) antiviral for picornaviruses 1
guanidine but very toxic antiviral for picornaviruses 1 2 3


Antiviral Mechanisms:

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

Fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of coxsackievirus RNA and protein. It might work by targeting the enterovirus 2C protein.
Pirlindole inhibits the RNA replication of coxsackieviruses and echoviruses. It likely works by targeting the enterovirus 2C protein. In a study, pirlindole was specifically shown to inhibit CVB replicons (non-cytolytic viruses).
• Curcumin potently inhibits coxsackievirus replication through dysregulation of the ubiquitin-proteasome system (UPS). Proteasome inhibitors reduce CVB replication via inhibition of viral RNA transcription and protein synthesis. 1
Itraconazole (Sporanox) is a broad spectrum anti-enterovirus compound that inhibits viral RNA replication by targeting oxysterol-binding protein. 1
OSW-1 is a potent broad spectrum anti-enterovirus compound that inhibits viral RNA replication by targeting oxysterol-binding protein. 1
Arbidol (umifenovir) decreased the CVB5 RNA level in infected host cells. 1
• Arbidol inhibits the high expression of IL-10 induced by CVB4; this IL-10 is key to the chronic persistence of CVB4, and Arbidol's IL-10 inhibition helps clear this virus. 1 More info in this post. Note that the antiviral tenofovir strongly inhibits IL-10. 1
• Ribavirin has a number of antiviral mechanisms, including causing lethal mutagenesis of the viral genome. 1
Dipyridamole has little or no antiviral activity, but is capable of remarkably enhancing the antiviral activity of IFN-α. 1
• Spatholobus suberectus extracts have remarkable anti-CVB3 activity in vitro. CVB3 messenger RNA (mRNA) is significantly inhibited by Spatholobus suberectus.
• 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.
• Hinokitiol imports zinc ions into the cell, which exerts antiviral effects by interfering with the viral life cycle.
Astragalus may inhibit the replication of CVB3 RNA

Note: when a study demonstrates a compound has antiviral efficacy against a specific enterovirus serotype, such as for example CVB3, that is because the study only investigated that particular serotype; but the same compound may potentially also have efficacy against other serotypes (but this is not known for sure).


General Notes:

Curcumin has a short half life of 3 to 6 hours, so you need to take curcumin 3 or 4 times a day.
• The anti-enteroviral compound in Emblica officinalis (amla) is called phyllaemblicin B. A study on phyllaemblicin B found it has strong antiviral effects against CVB3.
• The anti-enteroviral compound in Rhodiola rosea is called salidroside.
• The anti-enteroviral compound in Epimedium (horny goat weed) is called icariin. The icariin content of horny goat weed around 0% to 2.7%. 1
• The anti-enteroviral compounds in Sophora flavescens root (Ku Shen) are oxymatrine, matrine and sophoridine. As well as antiviral effects, oxymatrine and matrine also have an immunomodulatory action that can fight enteroviruses.
• 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 (this is by my calculations, based on data from the Aegle marmelos study). A study on the marmelide component from the herb Aegle marmelos (bael fruit) showed it is more potent than ribavirin against CVB1 to CVB6.
• A study on dihydroquercetin (a flavonoid supplement) show it is as strong or stronger than ribavirin in its antiviral effect against CVB4.
• A study on curcumin showed it is potently antiviral for CVB3.
• A study on the medicinal plants Dodonaea viscosa, Rumex nervosus and Rumex abyssinicus found they have strong activity against CVB3.
EGCG inhibits folate.
Emodin is a laxative.
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. The main antiviral compounds in this formula are forsythoside A, baicalin and chlorogenic acid. 1 2 Note that baicalin is not to be confused with baicalein (both are found in Scutellaria baicalensis). A study on Shuang Huang Lian found it was more potent than ribavirin.
Yakammaoto is a Chinese herbal formula containing 9 ingredients: Ephedra sinica, Pinellia ternate, Zingiber officinale, Tussilago farfara, Aster tataricus, Ziziphus jujube, Belamcanda chinensis, Asarum sieboldii, and Schisandra chinensis.
Isatis tinctoria is sometimes also called Isatis indigotica.
OSW-1 is a natural compound extracted from the bulbs of the plant Ornithogalum saundersiae that has been studied mainly for its anti-cancer activity.
Garlic is best not co-administered with Chinese skullcap. 1
Ursolic acid has a poor oral bioavailability of only 0.6%, 1 likely due to being metabolized by the gut wall and liver, as well as being poorly absorbed by the intestine. 1 An apple contains around 50 mg of ursolic acid in the peel. 1 Ursolic acid has been shown to damage DNA (although it also has an anti-cancer action), which is thought may constitute a serious problem. 1


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:

• Fluoxetine crosses the blood-brain barrier, and furthermore fluoxetine concentrates into the brain and central nervous system at levels 20 times higher than in the blood. So low oral doses of 20 to 40 mg of fluoxetine have been shown to produce high concentrations of 14 μM in the brain (much higher than its EC50 concentration of 2.3 μM). 1 However, the antiviral effects of fluoxetine are unfortunately not linearly dose dependent (see Fig 1 of this study), and it turns out that even a 30 μM concentration provides no more antiviral effect than 2.3 μM.
Oseltamivir
Dipyridamole
Lovastatin
Amantadine
• 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
Curcumin
Chlorogenic acid


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

In chronic infections, enteroviruses such as coxsackievirus B and echovirus can exist in two distinct forms: the regular lytic form of the virus (comprising viral particles), and a non-cytolytic form (comprising simply naked viral RNA), which lives inside cells as a chronic, smoldering intracellular infection. It is thought that as well as the lytic form, the non-cytolytic form of enterovirus may also play causal role in ME/CFS. 1

Since non-cytolytic enteroviruses comprise naked enteroviral RNA rather than the more usual viral particles, antivirals which work by viral particle entry inhibition or uncoating inhibition mechanisms will not have any direct effect on non-cytolytic enterovirus infections.

However, I believe that viral genome replication inhibitor antivirals will work for both lytic and non-cytolytic enteroviruses. And any antiviral that increases interferon alpha will I think fight non-cytolytic enteroviruses, because interferon alpha activates the intracellular immune response which targets such non-cytolytic infections.

In a study, pirlindole was specifically shown to inhibit CVB replicons (non-cytolytic viruses).

More information about non-cytolytic enteroviruses is given here.

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


EC50 Values of Antivirals:

When measuring the potency of an antiviral through in vitro experiments in cells lines, the EC50 (effective concentration) test is often used. The EC50 is the concentration of an antiviral compound in solution that will lead to a 50% reduction in viral replication in the cell line. The IC50 (inhibitory concentration) in the context of antivirals I believe is the same as EC50.

The EC50 is typically expressed in micrograms of the antiviral compound per milliliter of solution (μg/ml), or alternatively expressed in micromoles (μM). (To convert μM to μg/ml, multiply by the molecular weight, and divide by 1000).

Below are some EC50 figures for various antivirals tested in vitro. Note that the lower the EC50 figure, the stronger the antiviral.

The actual usefulness of an antiviral compound depends on its therapeutic index (aka: selectivity index), which is equal to the ratio: CC50 / EC50. Here, the CC50 is the cytotoxic concentration — the concentration of the antiviral that kills 50% of the cells in the cell line. For a useful antiviral, you obviously want the CC50 concentration to be quite a bit higher than the EC50.

EC50 Values for Antivirals (values shown in bold, and expressed as μg/ml). Note that smaller values represent a more potent antiviral:

Arbidol: HEp-2 cells: CVB3 = 13.1, HEp-2 cells: CVB5 = 6.6 1 2
Oseltamivir (Tamiflu): Vero cells: CVB3 = 6.8, CVB4 = 18 1
Raoulic acid: Vero cells: CVB3 = 0.33, CVB4 = 0.40 1
Ribavirin: HeLa cells: CVB3 = 1.9, Vero cells: EV5 = 22, EV18 = 7.6 1 2 3
Amantadine: Vero cells: EV5 = 1.0, EV18 = 5.0 1 2
Phyllaemblicin B (from Emblica officinalis): HeLa cells: CVB3 = 7.8 1
Marmelide (from Aegle marmelos): Vero cells: CVB1 to CVB6 = 63 (by comparison, study found ribavirin IC50 = 2000) 1
OSW-1: BGM cells: CVB3 = 0.002 1
Paris polyphylla extract: HeLa cells: CVB3 = 157 (by comparison, study found ribavirin IC50 = 129) 1
Baicalein (from skullcap herb): BGMK cells: CVB3 = 7.8 and SI = 34 (by comparison, study found ribavirin IC50 = 16 and SI = 15) 1
Ursolic acid: BCC-1/KMC cells: CVB1 = 0.4 (SI = 251); enterovirus 71 = 0.5 (SI = 201) 1


Indirubin derivative E804: and Akt Inhibitor IV: HeLa cells: 25 μM led to 2 log reduction in CVB3 1
Platelet-derived growth factor receptor tyrosine kinase inhibitor III (E5(1))
: HeLa cells: 25 μM led to 4 log reduction in CVB3 1


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 available.

TTP 8307 — potently inhibits CVB3 and poliovirus by interfering with the synthesis of viral RNA
V-073 / SCH-48973 (pocapavir) — capsid inhibitor for poliovirus, CVB and echovirus
GPC-N114 — RNA polymerase inhibitor, broad-spectrum anti-enterovirus, potent for CVB3 in vitro
Ro 09-0179 — flavone from Agastache rugosa, antiviral for rhinoviruses and CVB
SDZ 35-682 — a capsid-binding agent, potently inhibits several rhinoviruses and EV9
MDL-860 — broad-spectrum anti-picornavirus activity, including CVB3
TBZE-029 — inhibits CVB3, EV9, CVA9 and enterovirus 68
AG-7088 (rupintrivir) — rhinovirus protease inhibitor
R77975 (pirodavir) — rhinovirus inhibitor
LY-122772 (enviroxime) — rhinovirus and enterovirus inhibitor
WIN 63843 (pleconaril, Picovir) — a capsid-binding agent for rhinovirus and enterovirus
WIN 51711 (disoxaril) — rhinovirus and enterovirus inhibitor
T-705 (favipiravir, Avigan) — RNA polymerase inhibitor, antiviral for poliovirus and rhinovirus
BTA-798 (vapendavir) — inhibits rhinovirus
Rega Compound 17 — inhibits in vitro replication of CVB3, CVB4, CVB5 and CVB6
Rega Compound A — completely eradicates CVB4 from the tissues and organs of mice 1
androstenediol - any idea on where to
List of 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 chronic fatigue syndrome / myalgic encephalomyelitis (ME/CFS).

Note though that antiviral effects in vitro (in cell line tests) may not necessarily translate to effects in vivo (in the body), when the drug or supplement is taken orally. This is because with in vitro studies, they use a certain concentration of the drug or supplement in a cell line to achieve an antiviral effect. But that concentration may be too high to achieve in the body when the drug or supplement is taken orally.

Dr John Chia has found that the enteroviruses most commonly found as active infections in ME/CFS patients are: 1
  • CVB3 and CVB4 first and foremost
  • Then less frequently CVB2, EV6, EV7 and EV9; and then much less frequently EV11


Antiviral Drugs for Coxsackievirus B:

interferon alpha (immunomodulatory drug) for CVB3 1
ribavirin (antiviral drug) antiviral for CVB3 1
OSW-1 (saponin) broad-spectrum antiviral for enteroviruses including CVB3, poliovirus, rhinovirus 1
umifenovir
(Arbidol, Russian antiviral drug) antiviral for CVB3, CVB5 1 2 and CVB4 1
fluoxetine (antidepressant drug) antiviral for CVB1, CVB2, CVB3 1 2 and CVB4 1
pirlindole
(Pyrazidol, MAO-A antidepressant) antiviral for CVB3, and antiviral for other CVBs and echoviruses 1
dipyridamole (vasodilator) broad-spectrum antiviral for picornaviruses including CVB3 1 2
itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including CVB3, CVA16, poliovirus, enterovirus-71, enterovirus 68, rhinovirus 1 2
bosentan
(pulmonary hypertension drug) antiviral for CVB3 (and likely all CVBs) 1 More info here.
valsartan (ARB blood pressure drug) antiviral for CVB3 (and likely all CVBs) 1 More info here.
olmesartan (ARB blood pressure drug) antiviral for CVB3 1
lovastatin (statin drug) antiviral for CVB3 1
mycophenolate (immunosuppressive drug) antiviral for CVB3 1
oseltamivir (Tamiflu, antiviral for influenzavirus) antiviral for CVB3 and CVB4 1 (see Table 1 in the raoulic acid full paper)
amiloride (diuretic drug) antiviral for CVB3 1 2 3 4
arsenic trioxide (leukemia drug) antiviral for CVB3 1 2
glyceryl trinitrate and isosorbide dinitrate antiviral for CVB3 1
gemcitabine (chemotherapy drug) antiviral for CVB3 and CVB3 replicons (non-cytolytic CVB3) 1


Note that Dr John Chia found that interferon and ribavirin are effective against CVB3 and CVB5 infections, but found these drugs were not effective against CVB4 infections. 1 2


Antiviral Drugs for Echovirus:

ribavirin (antiviral drug) antiviral for EV5, EV11 and EV18 1 2 3
amantadine (antiviral drug) antiviral for EV5 and EV18 1 2
fluoxetine (antidepressant drug) antiviral for EV1, EV9 and EV11 1
itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including EV11 1 2
dipyridamole
(vasodilator) broad-spectrum antiviral for picornaviruses 1 2
pirlindole (Pyrazidol, MAO-A antidepressant) antiviral for echoviruses 1


Antiviral Supplements for Coxsackievirus B:

dihydroquercetin (DHQ, a flavonoid) is a antiviral (as good as ribavirin) for CVB4. 1 Used by Dr Chia.
Aegle marmelos (bael fruit, bilva) antiviral (as good as ribavirin) for CVB1 to CVB6 1
Emblica officinalis (Phyllanthus emblica, amla) root antiviral for CVB3 1 2
shuang huang lian
(Chinese herbal formula) antiviral for CVB3 1 2
garlic antiviral for CVB3 1
curcumin antiviral for CVB3 1
chlorogenic acid
(6% in coffee; 50% in green coffee bean) antiviral for CVB3 and CVB5 1 2
baicalein (from Scutellaria baicalensis, Chinese skullcap) antiviral for CVB3 1
Paris polyphylla (Qi Ye Yi Zhi Hua, Chong Lou) antiviral for CVB3 and enterovirus 71 1
raoulic acid (from Raoulia australis) antiviral for CVB3 and CVB4 1
Dodonaea viscosa (hopbush) antiviral for CVB3 1
oroxylin A
(from Scutellaria baicalensis) may be antiviral for CVB3 1 and for enterovirus 71 1
oxymatrine
(from Sophora flavescens root) immunomodulator for coxsackievirus B 1
ursolic acid antiviral for CVB1 and enterovirus 71 1
apigenin
antiviral for CVB1 and enterovirus 71 1
emodin
(from Japanese knotweed, aloe vera, rhubarb) antiviral for CVB3, CVB4 and CVB5 1 2 3
Spatholobus suberectus
(Ji Xue Teng) antiviral for CVB3 and CVB5 1 2 3 4
Sophora tonkinensis
(Shan Dou Gen) antiviral for CVB3 and CVB5 1
Terminalia chebula (haritaki, He Zi) antiviral for CVB3 and CVB5 1
Trichosanthes root (Tian Hua Fen, Chinese cucumber) antiviral for CVB3 1
Rhodiola rosea (golden root) antiviral for CVB3 1
Astragalus membranaceus antiviral for CVB3 1
Bupleurum (Chai Hu) antiviral for CVB1 1
Glycine max (black soybean extract, Dan Dou Chi) antiviral for CVB1 1
DHEA (dehydroepiandrosterone) protective during CVB4 infection 1
5-androstenediol 100 times more protective than DHEA during CVB4 infection 1 2 (more info)
sodium selenite (a form of selenium) antiviral for CVB5 1
Epimedium (horny goat weed) antiviral for CVB4 and CVB5 1 2 3
acemannan
(aloe polymannose from aloe vera leaves) antiviral for CVB3 1
Azadirachta indica (neem leaf) antiviral for CVB1 to CVB6 (but most effective for CVB4) 1
sophoridine (from Sophora flavescens root, Ku Shen) antiviral for CVB3 1 2
oxymatrine (from Sophora flavescens root, Ku Shen) antiviral for CVB3 and immunomodulator for coxsackievirus B 1 2
Isatis tinctoria (dyer’s woad, Da Qing Ye, Ban Lan Gen) antiviral for CVB3 1
Indirubin derivative E804
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
Quassia amara antiviral for CVB2 1
Rheum palmatum root (Chinese rhubarb, Turkish rhubarb) antiviral for CVB3 1
fatty acid synthase inhibitors (these include: amentoflavone, oleic acid, keemun tea, Parasitic loranthus, EGCG) are antiviral for CVB3 1 2
EGCG
(from green tea) antiviral for CVB3 1
clinoptilolite (a natural zeolite) antiviral for CVB5 1
selenium deficiency increases virulence of CVB3 1
vitamin E deficiency increases virulence of CVB3 1
copper deficiency increases virulence of CVB3 1
nicotinamide (aka: niacinamide, vitamin B3) antiviral for CVB4 and CVB5 1
ginsenosides antiviral for CVB3 1
wild berry fruit extracts antiviral for CVB1 1
berberine antiviral for CVB3 1
chrysin antiviral for CVB3 1
Re Du Ning antiviral for CVB3 1
Spirulina platensis antiviral for CVB4 1
Houttuynia cordata antiviral for CVB3 and CVB6 1
fucoidan antiviral for CVB4 1


Antiviral Supplements for Echovirus:

shuang huang lian (Chinese herbal formula) antiviral for EV11 1
garlic antiviral for EV11 1
oxymatrine (from Sophora flavescens root) immunomodulator for echovirus 1
betulin and betulinic acid (from birch bark and Chaga mushroom) antiviral for EV6 1
Spatholobus suberectus Dunn (Ji Xue Teng) antiviral for EV9 and EV29 1 2
Sophora tonkinensis
(Shan Dou Gen) antiviral for EV9 and EV29 1
latex from fig fruit (Ficus carica) antiviral for EV11 1
beta-lapachone (from Lapacho) antiviral for EV19 1
clinoptilolite (a natural zeolite) antiviral for EV7 1
lactoferrin antiviral for EV5 1
bismuth salts (such as bismuth subsalicylate) antiviral for EV12 1
Re Du Ning antiviral for EV11 1
serum albumin (of bovine and human origin) antiviral for EV7 and other echoviruses 1
EGCG (from green tea) antiviral for EV11 1


Antivirals for Enteroviruses and Picornaviruses in General:

lamivudine (Epivir) an antiviral used by Dr Chia for enterovirus infections, although he found Epivir is not effective for EV6 and EV7. 1
EGCG (extract from green tea) antiviral for enteroviruses 1
hinokitiol (found in hiba wood essential oil) antiviral for picornaviruses 1
guanidine but very toxic antiviral for picornaviruses 1 2 3


Antiviral Mechanisms:

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

Fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of coxsackievirus RNA and protein. It might work by targeting the enterovirus 2C protein.
Pirlindole inhibits the RNA replication of coxsackieviruses and echoviruses. It likely works by targeting the enterovirus 2C protein. In a study, pirlindole was specifically shown to inhibit CVB replicons (non-cytolytic viruses).
• Curcumin potently inhibits coxsackievirus replication through dysregulation of the ubiquitin-proteasome system (UPS). Proteasome inhibitors reduce CVB replication via inhibition of viral RNA transcription and protein synthesis. 1
Itraconazole (Sporanox) is a broad spectrum anti-enterovirus compound that inhibits viral RNA replication by targeting oxysterol-binding protein. 1
OSW-1 is a potent broad spectrum anti-enterovirus compound that inhibits viral RNA replication by targeting oxysterol-binding protein. 1
Arbidol (umifenovir) decreased the CVB5 RNA level in infected host cells. 1
• Arbidol inhibits the high expression of IL-10 induced by CVB4; this IL-10 is key to the chronic persistence of CVB4, and Arbidol's IL-10 inhibition helps clear this virus. 1 More info in this post. Note that the antiviral tenofovir strongly inhibits IL-10. 1
• Ribavirin has a number of antiviral mechanisms, including causing lethal mutagenesis of the viral genome. 1
Dipyridamole has little or no antiviral activity, but is capable of remarkably enhancing the antiviral activity of IFN-α. 1
• Spatholobus suberectus extracts have remarkable anti-CVB3 activity in vitro. CVB3 messenger RNA (mRNA) is significantly inhibited by Spatholobus suberectus.
• 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.
• Hinokitiol imports zinc ions into the cell, which exerts antiviral effects by interfering with the viral life cycle.
Astragalus may inhibit the replication of CVB3 RNA

Note: when a study demonstrates a compound has antiviral efficacy against a specific enterovirus serotype, such as for example CVB3, that is because the study only investigated that particular serotype; but the same compound may potentially also have efficacy against other serotypes (but this is not known for sure).


General Notes:

Curcumin has a short half life of 3 to 6 hours, so you need to take curcumin 3 or 4 times a day.
• The anti-enteroviral compound in Emblica officinalis (amla) is called phyllaemblicin B. A study on phyllaemblicin B found it has strong antiviral effects against CVB3.
• The anti-enteroviral compound in Rhodiola rosea is called salidroside.
• The anti-enteroviral compound in Epimedium (horny goat weed) is called icariin. The icariin content of horny goat weed around 0% to 2.7%. 1
• The anti-enteroviral compounds in Sophora flavescens root (Ku Shen) are oxymatrine, matrine and sophoridine. As well as antiviral effects, oxymatrine and matrine also have an immunomodulatory action that can fight enteroviruses.
• 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 (this is by my calculations, based on data from the Aegle marmelos study). A study on the marmelide component from the herb Aegle marmelos (bael fruit) showed it is more potent than ribavirin against CVB1 to CVB6.
• A study on dihydroquercetin (a flavonoid supplement) show it is as strong or stronger than ribavirin in its antiviral effect against CVB4.
• A study on curcumin showed it is potently antiviral for CVB3.
• A study on the medicinal plants Dodonaea viscosa, Rumex nervosus and Rumex abyssinicus found they have strong activity against CVB3.
EGCG inhibits folate.
Emodin is a laxative.
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. The main antiviral compounds in this formula are forsythoside A, baicalin and chlorogenic acid. 1 2 Note that baicalin is not to be confused with baicalein (both are found in Scutellaria baicalensis). A study on Shuang Huang Lian found it was more potent than ribavirin.
Yakammaoto is a Chinese herbal formula containing 9 ingredients: Ephedra sinica, Pinellia ternate, Zingiber officinale, Tussilago farfara, Aster tataricus, Ziziphus jujube, Belamcanda chinensis, Asarum sieboldii, and Schisandra chinensis.
Isatis tinctoria is sometimes also called Isatis indigotica.
OSW-1 is a natural compound extracted from the bulbs of the plant Ornithogalum saundersiae that has been studied mainly for its anti-cancer activity.
Garlic is best not co-administered with Chinese skullcap. 1
Ursolic acid has a poor oral bioavailability of only 0.6%, 1 likely due to being metabolized by the gut wall and liver, as well as being poorly absorbed by the intestine. 1 An apple contains around 50 mg of ursolic acid in the peel. 1 Ursolic acid has been shown to damage DNA (although it also has an anti-cancer action), which is thought may constitute a serious problem. 1


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:

• Fluoxetine crosses the blood-brain barrier, and furthermore fluoxetine concentrates into the brain and central nervous system at levels 20 times higher than in the blood. So low oral doses of 20 to 40 mg of fluoxetine have been shown to produce high concentrations of 14 μM in the brain (much higher than its EC50 concentration of 2.3 μM). 1 However, the antiviral effects of fluoxetine are unfortunately not linearly dose dependent (see Fig 1 of this study), and it turns out that even a 30 μM concentration provides no more antiviral effect than 2.3 μM.
Oseltamivir
Dipyridamole
Lovastatin
Amantadine
• 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
Curcumin
Chlorogenic acid


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

In chronic infections, enteroviruses such as coxsackievirus B and echovirus can exist in two distinct forms: the regular lytic form of the virus (comprising viral particles), and a non-cytolytic form (comprising simply naked viral RNA), which lives inside cells as a chronic, smoldering intracellular infection. It is thought that as well as the lytic form, the non-cytolytic form of enterovirus may also play causal role in ME/CFS. 1

Since non-cytolytic enteroviruses comprise naked enteroviral RNA rather than the more usual viral particles, antivirals which work by viral particle entry inhibition or uncoating inhibition mechanisms will not have any direct effect on non-cytolytic enterovirus infections.

However, I believe that viral genome replication inhibitor antivirals will work for both lytic and non-cytolytic enteroviruses. And any antiviral that increases interferon alpha will I think fight non-cytolytic enteroviruses, because interferon alpha activates the intracellular immune response which targets such non-cytolytic infections.

In a study, pirlindole was specifically shown to inhibit CVB replicons (non-cytolytic viruses).

More information about non-cytolytic enteroviruses is given here.

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


EC50 Values of Antivirals:

When measuring the potency of an antiviral through in vitro experiments in cells lines, the EC50 (effective concentration) test is often used. The EC50 is the concentration of an antiviral compound in solution that will lead to a 50% reduction in viral replication in the cell line. The IC50 (inhibitory concentration) in the context of antivirals I believe is the same as EC50.

The EC50 is typically expressed in micrograms of the antiviral compound per milliliter of solution (μg/ml), or alternatively expressed in micromoles (μM). (To convert μM to μg/ml, multiply by the molecular weight, and divide by 1000).

Below are some EC50 figures for various antivirals tested in vitro. Note that the lower the EC50 figure, the stronger the antiviral.

The actual usefulness of an antiviral compound depends on its therapeutic index (aka: selectivity index), which is equal to the ratio: CC50 / EC50. Here, the CC50 is the cytotoxic concentration — the concentration of the antiviral that kills 50% of the cells in the cell line. For a useful antiviral, you obviously want the CC50 concentration to be quite a bit higher than the EC50.

EC50 Values for Antivirals (values shown in bold, and expressed as μg/ml). Note that smaller values represent a more potent antiviral:

Arbidol: HEp-2 cells: CVB3 = 13.1, HEp-2 cells: CVB5 = 6.6 1 2
Oseltamivir (Tamiflu): Vero cells: CVB3 = 6.8, CVB4 = 18 1
Raoulic acid: Vero cells: CVB3 = 0.33, CVB4 = 0.40 1
Ribavirin: HeLa cells: CVB3 = 1.9, Vero cells: EV5 = 22, EV18 = 7.6 1 2 3
Amantadine: Vero cells: EV5 = 1.0, EV18 = 5.0 1 2
Phyllaemblicin B (from Emblica officinalis): HeLa cells: CVB3 = 7.8 1
Marmelide (from Aegle marmelos): Vero cells: CVB1 to CVB6 = 63 (by comparison, study found ribavirin IC50 = 2000) 1
OSW-1: BGM cells: CVB3 = 0.002 1
Paris polyphylla extract: HeLa cells: CVB3 = 157 (by comparison, study found ribavirin IC50 = 129) 1
Baicalein (from skullcap herb): BGMK cells: CVB3 = 7.8 and SI = 34 (by comparison, study found ribavirin IC50 = 16 and SI = 15) 1
Ursolic acid: BCC-1/KMC cells: CVB1 = 0.4 (SI = 251); enterovirus 71 = 0.5 (SI = 201) 1


Indirubin derivative E804: and Akt Inhibitor IV: HeLa cells: 25 μM led to 2 log reduction in CVB3 1
Platelet-derived growth factor receptor tyrosine kinase inhibitor III (E5(1))
: HeLa cells: 25 μM led to 4 log reduction in CVB3 1


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 available.

TTP 8307 — potently inhibits CVB3 and poliovirus by interfering with the synthesis of viral RNA
V-073 / SCH-48973 (pocapavir) — capsid inhibitor for poliovirus, CVB and echovirus
GPC-N114 — RNA polymerase inhibitor, broad-spectrum anti-enterovirus, potent for CVB3 in vitro
Ro 09-0179 — flavone from Agastache rugosa, antiviral for rhinoviruses and CVB
SDZ 35-682 — a capsid-binding agent, potently inhibits several rhinoviruses and EV9
MDL-860 — broad-spectrum anti-picornavirus activity, including CVB3
TBZE-029 — inhibits CVB3, EV9, CVA9 and enterovirus 68
AG-7088 (rupintrivir) — rhinovirus protease inhibitor
R77975 (pirodavir) — rhinovirus inhibitor
LY-122772 (enviroxime) — rhinovirus and enterovirus inhibitor
WIN 63843 (pleconaril, Picovir) — a capsid-binding agent for rhinovirus and enterovirus
WIN 51711 (disoxaril) — rhinovirus and enterovirus inhibitor
T-705 (favipiravir, Avigan) — RNA polymerase inhibitor, antiviral for poliovirus and rhinovirus
BTA-798 (vapendavir) — inhibits rhinovirus
Rega Compound 17 — inhibits in vitro replication of CVB3, CVB4, CVB5 and CVB6
Rega Compound A — completely eradicates CVB4 from the tissues and organs of mice 1

@Hip

5-androstenediol 100 times more protective than DHEA during CVB4 infection 1 2 (more info) can't find this anywhere, any idea's? DHEA helps but makes me aggressive 😩
 

Hip

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Has anyone here tried - Interferon Alfa-2b suppositories? As Chia has used this IV with some of his patients.
Some years ago, I found interferon suppositories cheaply available from Russian international online pharmacies, and I proposed that interferon alpha suppositories might work very well for enterovirus ME/CFS. This is because suppositories are immune from the loss of effect that eventually occurs with injected interferon.

See this post for more details. Dr Chia found interferon works for CVB3 and CVB5, but he observed it is not effective for CVB4. So if you have high titers to either CVB3 or B5 on the ARUP Lab coxsackievirus B antibody tests, then interferon alpha suppositories is something you can consider trying.
 
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The quality of recombinant interferon is very important. In Russia, the quality is very poor. It causes inflammation due to impurities from other components in its production.
 
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The quality of recombinant interferon is very important. In Russia, the quality is very poor. It causes inflammation due to impurities from other components in its production.
That is sad to hear. Is it like that with ALL brands? Also does that also include Ribavirin capsules(have purchased few bottles)?
 

Hip

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The quality of recombinant interferon is very important. In Russia, the quality is very poor. It causes inflammation due to impurities from other components in its production.
Is that something you read somewhere?

Even if true, these impurities may not be an issue if you are taking the interferon as a suppository, as the rectal mucous membranes may filter out the impurities.

Impurities are also an issue with Western interferon: with injected interferon made by US or European pharmaceutical companies, after some time administering it, the body may develop antibodies which attack and disable the interferon (this is the reason injected interferon usually loses its effect if you keep using it).

I am not sure why these antibodies develop, but my guess it is because interferon is manufactured by a recombinant process using bacteria to synthesize it, and so you may get some bacterial proteins mixed in with your interferon product. I suspect these bacterial proteins will eventually trigger an immune antibody response to the recombinant interferon.

But if you administer interferon as a suppository, you don't get the problem of these antibodies appearing. You can use rectally administered interferon indefinitely, without it being disabled by antibodies. I am guessing that interferon as a suppository is free of the antibody problem because the bacterial proteins in the interferon will be filtered by the rectal mucous membranes.
 

Pyrrhus

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Also does that also include Ribavirin capsules
I would caution against trying Ribavirin for enteroviruses. Due to its mechanism of action, Ribavirin has a decidedly nonlinear dose-response curve that is more like a step function.

In other words, if the dosage is above the threshold dosage, the virus will be suppressed. But if the dosage is below the threshold dosage, the virus will not be suppressed at all. (and may even be stimulated to replicate!)

Unfortunately, at the threshold dosage for enteroviruses, Ribavirin causes serious bone-marrow suppression. This bone-marrow suppression will lead to a profound immune deficiency, and can be very serious.

Hope this helps.
 
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I would caution against trying Ribavirin for enteroviruses. Due to its mechanism of action, Ribavirin has a decidedly nonlinear dose-response curve that is more like a step function.

In other words, if the dosage is above the threshold dosage, the virus will be suppressed. But if the dosage is below the threshold dosage, the virus will not be suppressed at all. (and may even be stimulated to replicate!)

Unfortunately, at the threshold dosage for enteroviruses, Ribavirin causes serious bone-marrow suppression. This bone-marrow suppression will lead to a profound immune deficiency, and can be very serious.

Hope this helps.
Is there a way to utilize 120 x 200mg capsules or at least information relating to those details?