• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Arbidol; a novel Antiviral and Immunomodulator

eljefe19

Senior Member
Messages
483
Thanks to @halcyon and @Hip I've been turned onto the Russian atypical antiviral, Arbidol.
I've compiled two relevant studies explicating the immuno-modulatory effects of Arbidiol.


"In vitro, antiviral and immunomodulatory activity of Arbidol and structurally related derivatives in HSV1-infected Human Keratinocytes."

An efficient elimination of the viral infection requires a pro-inflammatory host response and development of T helper (Th)1-type immunity ( Arena et al., 2010 ; Lucey et al., 1996 ; Romagnani, 1997 ). Mogensenet al. (2004) demonstrated that after early induction of the pro-inflammatory host response, HSV-1 down-regulates the pro-inflammatory cytokine production through the accumulation of two VPs, ICP4 and ICP27, whose transcription is induced by the release of tegumental protein VP16. By destabilizing the mRNAs of pro-inflammatory genes, these VPs delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins ICP0 and VP16 induce the expression of the IL-10 and transforming growth factor (TGF)-β immunosuppressive cytokines. The up-regulation in the expression of IL-10 and TGF-β induced by HSV-1 in keratinocytes can be considered part of the viral strategy to avoid local immune defence mechanisms in the skin and to promote the establishment and maintenance of infection ( Zak-Prelich et al., 2001 ).

Cell lysates collected from HaCat cells at 3 and 6 h post-infection ( Figs 3 and 4 , respectively), in the presence or absence of ARB or its analogues, were tested for VP16 and ICP27 viral protein expression. ARB and its derivatives significantly reduced the levels of VP16 protein expression after 3 h of infection compared to HSV-1 alone, and the reduction was more marked after 6 h of treatment. This reduction was more intense with the analogues compared to that obtained with ARB treatment. In addition, the HSV-1-induced ICP27 protein expression was reduced by ARB and the analogues tested only after 6 h of infection. A small amount of constitutive VP16 protein was detected in the mock-infected cells at 3 h compared to untreated cells.

In other beneficial ME/CFS medications such as Cimetidine, a key component is the decreasing of IL-10.
TGF-B is also immunosuppressive according to the above study, so reducing it is most likely beneficial as well. I believe the immuno-modulatory effects are what ultimately make this an effective drug, on paper, for ME/CFS. Case in point, the following study; (props to @halcyon).


CVB4 Arbidol study


Coxsackie virus cannot be completely eliminated due to restrictive replication and impaired immune response, thus causing persistent infection. IL-10 plays a decisive role in the course of persistent viral infection. Umifenovir (Arbidol) is a broad-spectrum antiviral drug, with certain treatment effects on Coxsackie virus infection. Previously, we showed that in addition to inhibiting Coxsackie B4 (CVB4) infection, Umifenovir also down-regulates IL-10 induced by persistent CVB4 virus infection in vitro and in vivo. Here, BALB/c mouse spleen cells infected with CVB4 were used as a model to explore the mechanism by which Umifenovir affects IL-10 expression. We found that subcellular localization of p38 and MAPK-activated protein kinase 2 (MK2) played a very important role in IL-10 secretion, and Umifenovir significantly prevented p38-MK2 complex from exiting the cell nucleus. This in turn blocked the biological functions of the latter pathway, and inhibited the high expression of IL-10 induced by CVB4. These findings suggest that Umifenovir is a potential anti-CVB4 drug; most importantly, Umifenovir could be used to treat IL-10 induced persistent viral infection.


I have some low to mid viral titers across the board, tried Valcyte, was a non-responder, and haven't taken any traditional AV's since. Just oxymatrine and others th1 cytokine inducing immune boosters. However, I've purchased Arbidiol and apparently will be the first guinea pig for the community. Wish me luck! Hope some of you found this interesting! Especially....if you have suspected chronic enterovirus infection.
Peace and love yall
 

eljefe19

Senior Member
Messages
483
Looking more closely at this CVB4 Arbidol study, and mechanism by which Arbidol (umifenovir) reduces the IL-10 secretion caused by CVB4, the full paper says that:


So if we can further boost p38 phosphorylation (p38 activation) and reduce MK2 phosphorylation (MK2 activation) by other means as well, that may help even more to shift from Th2 to Th1 in the case of chronic coxsackievirus B4 infection.

MK2 = MAPK-activated protein kinase 2.

Seems that insulin boosts p38 activation in smooth muscle cells (so perhaps the intranasal insulin I was experimenting with might have an antiviral effect in the brain), as does follicle stimulating hormone (ref: 1).

Added by @Hip in a previous discussion.
 
Messages
38
N=1 number 2, we have also started a trial of Arbidol.

The patient is my wife, who has a confirmed persistent Coxsackie B-4 infection in the muscle wall of her small bowel. This was confirmed by Dr. Chia by both Arup blood testing (Coxsackie B-4 value of greater than 1:640) and analysis of a biopsy of her small intestine removed during bowel surgery. The biopsy showed enteroviral infection in greater than 50% of the cells in one layer of muscle. She has had symptoms of this for over 6 years, starting with continuous high nausea and now also including brain fog, POTS, PEM, periodic pseudo bowel obstructions and general malaise. She is currently bedridden 23 hours a day and on a very restricted diet to prevent a small bowel obstruction. Her only current CFS treatment is IVIG as per a recommendation from Dr. Chia, she has had 6 IG infusions with no improvement yet. That is our baseline.

Arbidol looks like a perfect drug for us, here is the best source for information in English that I can find-

http://www.arbidol.org/index.html


here is the dosing information in English-

http://www.arbidol.org/instructions-for=arbidol.pdf


A couple of things jumped out to me- the time to max serum levels is very short, 1.5 hours, so frequent dosing throughout the day looks to be the best idea. Arbidol is metabolized in the liver so it is excreted through the bile and shows up in the stool, this means that there will be Arbidol available in the intestinal tract to be absorbed transdermally into the intestinal wall, I just don't know if it is able to be absorbed transdermally.

We purchased our Arbidol from here - http://www.rumedstore.com/Arbidol/cat4363362_3558888.aspx mostly because they accept Paypal so I didn't have to mess with wire transfers. I ordered on 3-9-17, it was shipped on 3-10 and it showed up in Colorado on 3-27. I bought both 50 mg tablets and 100 mg capsules so we can dose anywhere from 12.5mg (¼ tablet) up to 200 mg or more.

Beginning 3-27 we started with a 3 day trial at 50mg and then a pause for a couple of days to check for reactions. We then went to 50mg daily for several more days until she began to have what is commonly called a herx reaction but is probably more accurately some sort of an IRIS response. We have been trying various dosage and frequency schedules to find something we can work with, right now we are using 25mg every other day.

I will post updates every so often, both of progress and of failure.
 

Hip

Senior Member
Messages
17,820
Good luck with your testing of Arbidol for coxsackievirus B4. I also have a chronic active coxsackievirus B4 infection, and I think this CVB4 is most likely the virus that triggered my ME/CFS.

Did your wife show signs of chronic viral symptoms right from time she first caught the virus? When I caught my virus, even before I developed ME/CFS, it causes chronic throat, nasal, stomach and intestinal symptoms, as well as some nasty mental symptoms (as the virus seemed to affect my brain). Not only that, but as my virus spread to friends and family, it caused these same chronic symptoms in a number of people.

More info on my virus on my website here: https://chronicsorethroat.wordpress.com



One antiviral treatment for coxsackievirus B you may like to consider is high dose selenium. Selenium has antiviral properties in the case of chronic coxsackievirus B infections. You can read details of the high dose selenium protocol I use here:

High Dose Selenium Significantly Improves My Fatigue and Brain Fog

This simple selenium treatment was the single most effective intervention I have found for my ME/CFS. And it works fast too: the improvements in my fatigue and brain fog began to manifest after around 10 days of taking 400 mcg of selenium daily on an empty stomach. Every time I stop selenium, my ME/CFS begins to get worse within a matter of days.

As your wife also has CVB4, I thought I'd mention my success with selenium, as conceivably it might help her too.



A couple of things jumped out to me- the time to max serum levels is very short, 1.5 hours, so frequent dosing throughout the day looks to be the best idea.

It is the half life of a drug or supplement in the body that actually determines how frequently you need to dose a drug. (The half is the time it takes for the blood levels of the drug to drop by half). In the case of Arbidol, the half life is quite long, 17-21 hours. Ref: here.

So that means you only really to re-dose Arbidol once or twice a day, from the perspective of keeping up the blood levels of the drug. (Sometimes with drugs or supplements, you get short half lives of around 6 hours, which means that dosing three times a day is necessary in order to keep up blood levels).
 
Last edited:

Mary

Moderator Resource
Messages
17,321
Location
Southern California
@Hip - I have positive titers for Coxsackie B also. I never had the emotional symptoms you did, though I did have a chronic sore throat with accompanying fatigue for several years, particularly a couple of years before the onset of PEM, and for a few years thereafter.

Many years ago my doctor had me start taking 200 mcg. selenium a day because of its anticancer properties, so I'm wondering if this may have helped protect me from some of the worst manifestations of the virus. I have no idea what my titers are now, and I don't get the sore throat any more, but it's very good to know about selenium if it recurs.
 

Hip

Senior Member
Messages
17,820
Many years ago my doctor had me start taking 200 mcg. selenium a day

I found that 400 mcg daily made a much more noticeable improvement in my ME/CFS than 200 mcg, so it seems that this higher dose level is important— at least that's what I found. 400 mcg is still within the maximum recommended daily dose.

I was headed into severe ME/CFS territory before starting selenium: I'd be in bed all day for at least one day a week, and be sleeping 14 hours a day on most other days (including daytime naps). But after selenium, I improved to moderate ME/CFS, edging towards mild ME/CFS.

Be aware that some forms of selenium have lower bioavailability than others. I typically use yeast-free selenomethionine, which has near 100% absorption in the gut (when taken on an empty stomach). But other forms of selenium like selenate or selenite have only around 50% absorption. So if you take 400 mcg of selenium selenate, you may only be getting around 200 mcg absorbed in your body.

Se-methylselenocysteine is another form of selenium with high bioavailability, and Swanson do a well priced Se-methylselenocysteine product called SeMSC Selenium, which is what I am using at present. From HealthyMonthly, this costs only around £5 for 120 x 200 mcg.
 

Sancar

Sick of being sick ~
Messages
98
Location
So Cal USA
N=1 number 2, we have also started a trial of Arbidol.

The patient is my wife, who has a confirmed persistent Coxsackie B-4 infection in the muscle wall of her small bowel. This was confirmed by Dr. Chia by both Arup blood testing (Coxsackie B-4 value of greater than 1:640) and analysis of a biopsy of her small intestine removed during bowel surgery. The biopsy showed enteroviral infection in greater than 50% of the cells in one layer of muscle. She has had symptoms of this for over 6 years, starting with continuous high nausea and now also including brain fog, POTS, PEM, periodic pseudo bowel obstructions and general malaise. She is currently bedridden 23 hours a day and on a very restricted diet to prevent a small bowel obstruction. Her only current CFS treatment is IVIG as per a recommendation from Dr. Chia, she has had 6 IG infusions with no improvement yet. That is our baseline.

Arbidol looks like a perfect drug for us, here is the best source for information in English that I can find-

http://www.arbidol.org/index.html


here is the dosing information in English-

http://www.arbidol.org/instructions-for=arbidol.pdf


A couple of things jumped out to me- the time to max serum levels is very short, 1.5 hours, so frequent dosing throughout the day looks to be the best idea. Arbidol is metabolized in the liver so it is excreted through the bile and shows up in the stool, this means that there will be Arbidol available in the intestinal tract to be absorbed transdermally into the intestinal wall, I just don't know if it is able to be absorbed transdermally.

We purchased our Arbidol from here - http://www.rumedstore.com/Arbidol/cat4363362_3558888.aspx mostly because they accept Paypal so I didn't have to mess with wire transfers. I ordered on 3-9-17, it was shipped on 3-10 and it showed up in Colorado on 3-27. I bought both 50 mg tablets and 100 mg capsules so we can dose anywhere from 12.5mg (¼ tablet) up to 200 mg or more.

Beginning 3-27 we started with a 3 day trial at 50mg and then a pause for a couple of days to check for reactions. We then went to 50mg daily for several more days until she began to have what is commonly called a herx reaction but is probably more accurately some sort of an IRIS response. We have been trying various dosage and frequency schedules to find something we can work with, right now we are using 25mg every other day.

I will post updates every so often, both of progress and of failure.
 
Messages
38
The IVIG was started at 10g., increased to 20g. and is now at 30g. which her Dr. considers a full dose, she weighs about 115 lbs.

We tried selenium at 400 mcg. per day for 60 days with no improvement, I have her on 200 mcg. per day now.

Here is a paper with a plasma concentration graph on page 5 ( http://www.arbidol.org/arbidol-2006-human-plasma.pdf ), the curve is pretty steep in and out with a long tail. The 17-21 hour number is the reason I'm using every other day dosing to start, that way we don't stack the dosage over several days. I noticed that the dosing directions call for 200mg. four times a day for some viral situations so I'm guessing to maximize blood levels frequent dosing is needed. The IL-10 CVB4 study showed relative high concentrations are needed to fully inhibit the CVB4, I emailed one of the authors to see if she could provide me with an English translation of the prior study they mentioned in the IL-10 study but I've never heard back.

My wife's onset was complicated, she had complications from a back surgery and was on high doses of opioids and methadone. When she came off the painkillers she was left with the nausea, we spent several years chasing various explanations before we came to CFS and then the viral infection. Initially she was just nauseous, after several years she had spiraled down to full blown CFS. Dr. Chia proposed that she ate some bad mussels in Baltimore while receiving medical treatment at Johns Hopkins, there was a brief episode of "stomach flu" around then. She now has the full compliment of mental/brain symptoms including periods of slow thinking, memory loss, anxiety, depression and headaches. Our biggest concern is she has daily episodes of abdominal swelling when her small bowel "paralyzes" for awhile .

We did create almost full remission a couple of years ago with a combination of an herbal anti viral and GCMAF injections, unfortunately she over exerted and regressed and we could never replicate the success. I'm hoping that the IL-10 pathway will replicate the GCMAF component of our success.
 

Hip

Senior Member
Messages
17,820
She now has the full compliment of mental/brain symptoms including periods of slow thinking, memory loss, anxiety, depression and headaches. Our biggest concern is she has daily episodes of abdominal swelling when her small bowel "paralyzes" for awhile .

I found N-acetyl-glucosamine (NAG) and several other supplements highly effective for the anxiety induced by my viral symptoms. More info here. I had moderate to severe anxiety, but these supplements more or less eliminated it.

NAG also has benefits for the intestines: it supports the intestinal mucous membranes, according to this article.

Might leaky gut be involved in the abdominal swelling symptoms? Some info about leaky gut in this thread.

Enterovirus can also affect the nerves of the intestines, which can then cause intestinal symptoms.

Did Dr Chia try oxymatrine / Equilibrant? That works well for some ME/CFS patients with enterovirus infections.
 

Charles555nc

Senior Member
Messages
572
Has anyone been able to find an interferon suppository outlet (usually russian as well) that accepts pay pal? I checked that link for arbidol and am trying to order all the stuff together so I can do my own trial.
 

halcyon

Senior Member
Messages
2,482
Has anyone been able to find an interferon suppository outlet (usually russian as well) that accepts pay pal? I checked that link for arbidol and am trying to order all the stuff together so I can do my own trial.
I haven't found one that accepts paypal, no. I ordered some viferon from http://pharmashipping.net/ but it has yet to arrive. I previously ordered some isoprinosine successfully from them, so I'm worried it got hung up somewhere in shipping.