A New Candidate for Anti-Enteroviral Drug

[Steve4Andrea]

I have two things to offer- a new study and a story.

Antiviral activity of micafungin against enterovirus 71

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907259/

Be sure to look at Additional File 6, it describes the reduced response to Coxsakie B-3.

And now the story-

About 5 years ago before we had even heard of CFS and we were still trying to figure out what was going on with my wife I became convinced that she could have a fungal infection in her bile ducts, there were a number of reasons I believed this and had some Dr.s who agreed but most did not. I eventually wrote to a Dr. who had authored a study on this condition and he called me at home one Friday night.

His recommendation (his words were "if she was my patient...") was 30 days of Fluconazole and if that didn't work we'd have to try IV anti-fungals. We did the 30 days and no change so I went looking for a Dr. to treat her with an IV anti-fungal, which I found. The IV drug we chose for several reasons was Micafungin .

She was given an IV dose daily for 2 weeks, at the end she felt better. Most importantly her body weight went from 93 lbs. before treatment to 99 lbs. 6 weeks after treatment and her resting heart rate went from 130 before treatment down to 105 after (this was before we had ever heard of POTS). Unfortunately it did not "cure" her and she continued to decline after a period of time although her body weight has remained normal (for her 110 lbs.) since then.

I have always believed she had the fungal infection but since then she has been diagnosed by Dr. Chia with a Coxsakie B4 infection in the muscles of her small bowel. This study is newly published, I have a call into Dr. Chia to schedule a phone conference to discuss it with him.

 

[Hip]

Antivirals that work for enterovirus 71 probably will not work for the enteroviruses linked to ME/CFS (which are coxsackievirus B and echovirus), so it's unlikely micafungin will be of much use in enterovirus-associated ME/CFS.

Though this discovery may be very useful for the enterovirus 71 outbreaks that appear in Asian countries, and kill many children.



EDIT: Sorry, I did not see the bit about the effects of micafungin against coxsackievirus B3.

Though the study says that:

Micafungin potently inhibited the proliferation of EV71 in LLC-MK2 Derivative cells and moderately inhibited that of Coxsackievirus B3 (CVB3) in HeLa cells.

So although micafungin has strong effects against EV71, its effect against CVB3 is only moderate. Usually unless you have potent antiviral effects, an antiviral is not of much use.

And even where are potent antiviral effects, it may not be a great help for ME/CFS. I compiled a list of coxsackievirus B and echovirus antivirals in this post. Some you can see are potent, but having tried many of these, they have not helped my CVB4-associated ME/CFS that much (although I only took them on a short term basis for a week or so; a longer test would be necessary).

 

[Steve4Andrea]

I understand the difference between EV71 and the Coxsakie's, EV71 seems popular for study both because of the severity of the illness and the availability of the strain for research. Coxsakie 3 appears to be the most accessible for research of the CVB strains and I don't know how it's response's compares to CVB4 (CVB4 is also the infection we are fighting). The referenced "Additional File 6" shows about 50% effectiveness against CVB3 at max concentration, not great but still a possibility. I don't remember what the toxicity of Micafungin was so I don't know if it could be used at higher dosages, until we have a Dr. willing to administer it the question is mute.

I'm familiar with your posting on herbals and as time permits I'm putting together a post on my experiences with herbal antivirals for CVB4, some promising results and some new trials.

 

[Hip]

The referenced "Additional File 6" shows about 50% effectiveness against CVB3 at max concentration

That is not actually a direct measure of the antiviral efficacy, though.

The usual way you measure the efficacy of antivirals is first determining the concentration of an antiviral compound that will lead to a 50% reduction in viral replication (this is called the IC50 concentration), as the "Additional File 6" shows. This is done in a human cell line, not in vivo.

Usually if you increase the concentration of your antiviral compound further, you get a greater reduction in viral replication. But as you increase the concentration more and more to get a stronger and stronger antiviral effect, you reach a point where the antiviral compound starts to have toxic effects on the human cells themselves (cytotoxic effects). So obviously these cytotoxic effects put a maximum limit on the concentration and dosage of the antiviral, as you can't have an antiviral dose so high as to cause cell damage or cell death.

Cytotoxic effects on cells are usually measured by the CC50 concentration, which I believe is defined as the concentration of an antiviral compound which kills 50% of the cells in your cell line.

It is this CC50 concentration which in combination with the IC50 that determines the actual effectiveness of an antiviral, because you have to keep the antiviral concentration slightly lower than the level where it starts to cause toxic effects on cells.

So a useful antiviral compound has its antiviral IC50 concentration much lower than its CC50 cytotoxic concentration. To quantify just how much lower the IC50 concentration is compared to the CC50 concentration, we use the selectivity index (also called the therapeutic index):

The selectivity index of an antiviral is defined as = CC50 / IC50.

As an example, the selectivity index of ribavirin is 35.

The higher the selectivity index number, the better the antiviral, because it means you can use higher doses without worrying about cytotoxic effects.



I've read quite a few studies on enterovirus antivirals, and usually the authors will use words such as "potent" or "strong" if they find an antiviral compound that qualifies for such adjectives.

Or sometimes in studies they will compare the antiviral efficacy of the compound under investigation against the standard enterovirus antiviral ribavirin, and then the authors will state something like "this compound was comparable in potency to ribavirin."

 

[Hip]

By the way, if you are in touch with Dr Chia, one thing I have always been curious about is why, as far as I am aware, he does not use ribavirin on his patients.

If you look at this study by Dr Chia, it says:

Seven patients had marked improvement of fatigue and other flu-like symptoms within 2 to 3 weeks of taking ribavirin. Mild headaches and nausea were the most common side effects.

Six patients relapsed with recurrence of all of the symptoms of CFS within 1 to 2 weeks of drug discontinuation. All seven patients had a fourfold or greater reduction of neutralizing antibody during treatment.

So as far as I can see, ribavirin might be a reasonable treatment for enterovirus-associated ME/CFS, provided that you take this drug indefinitely.

Though on a video of Dr Chia (see timecode 42:31), he said that the combination of interferon and ribavirin is effective against coxsackievirus B3 infections, but he said he found these drugs were not effective against coxsackievirus B4 infections.

So possibly ribavirin does not work for CVB4.

 

[Steve4Andrea]

Micafungin is a dead end for us, I spoke with Dr. Chia and he declined to pursue it because there were no human trials in the study. I then spoke with two other Infectious Disease Dr.'s both whom also declined to treat with it. We have now moved on to Arbidol- http://forums.phoenixrising.me/inde...-a-novel-antiviral-and-immunomodulator.50047/

 

[max_yazhbin]

@Steve4Andrea can you tell me which doctor prescribed IV micafungin, I am trying to get it but despite having candida IgG and IgA in my blood and lumps in my neck among other symptoms, my doctors keep pretending to care.