It does look like a potent antiviral drug in your table, wonder why it didnt lower viral titers on the Chia's patients?
Pleconaril lowered antibody levels on one patient, as
the study indicates, but not the three others who tried it:
Four patients with CFS and either persistently raised antibody titres for CVB or echoviruses and/or positive enteroviral RNA of the peripheral blood leucocytes were treated with Pleconaril, an anti-capsid agent specific for uncoating of enterovirus and rhinovirus, obtained through a compassionate use protocol of Viropharma Inc, Exton, Pennsylvania, USA.
Three patients had no symptomatic improvement while on or after one week of drug treatment, at a dose of 400 mg three times a day, and there was no change of antibody titre after the treatment.
One patient had a moderate symptomatic improvement while taking Pleconaril 200 mg three times a day for one month, along with a fourfold decrease of antibody titres for CVB4 and echoviruses 7 and 11.
However, she relapsed about one month later, and did not respond to a further month of treatment. As of March 2004, the oral form of Pleconaril is no longer available for investigational use.
If you look at the Potency Factors in my table above, you see that the antiviral potency varies widely from enterovirus to enterovirus, with this drug having low (red) or moderate (orange) potency for some enteroviruses, and high (green) potency for other enteroviruses. Even for the same enterovirus serotype, potency varies even for different strains of that virus.
So it could be that the patients who failed to respond to pleconaril were those who had enteroviruses which this drug only has weak potency for.
In other words, for enterovirus ME/CFS patients trying pleconaril, it would be a matter of luck whether this drug is able to have any antiviral effect on the particular viruses they have.
If Ribavirin, Epivir and Interferons show more effect on his patients, wonder what is their pharmacokinetic values.
Using
Epivir (lamivudine) off-label to treat enterovirus was Dr Chia's idea. There is no in vitro data for the antiviral effect of Epivir for enterovirus, so no pharmacokinetic calculation can be performed.
We know from Dr Chia's reports that Epivir works for about 1 in 3 enterovirus ME/CFS patients. But even when it does work, the benefits are not major. It is not the sort of drug which will typically move you up one level on the ME/CFS scale of
severe, moderate, mild, remission.
Whereas drugs like
oxymatrine and
tenofovir, which are used by Dr Chia, can move patients up 1 level on that scale, if the patient is lucky enough to have these drugs work for them.
I believe the main three drugs Dr Chia uses for enterovirus ME/CFS are oxymatrine, tenofovir and Epivir, so enterovirus patients might consider trying all of these, one by one.
I tried oxymatrine and Epivir with no effect. I started taking tenofovir but got substantial mental health worsening. I tried tenofovir twice, but the same side effect occurred. So at present I am unable to try tenofovir, but if I can improve brain health and make my mental health more robust, I will hopefully be able to try tenofovir in future.
I know one ME/CFS patient with CVB4, the same virus as mine, who experienced permanent improvements from tenofovir after just a few months treatment. He said tenofovir completely eliminated his PEM, and it remained eliminated even after stopping tenofovir. Another patient trying tenofovir also got permanent improvements from it.
This ability to provide
permanent improvements is very significant, because often you find with ME/CFS that antivirals help, but patients relapse after stopping the drug (as we saw above with pleconaril). But the two tenofovir success stories I know (detailed in the
recoveries thread) both resulted in
permanent improvements which remained after stopping the drug.
Tenofovir is also used off-label for enterovirus by Dr Chia, and there is no in vitro data for the antiviral effect of tenofovir on enteroviruses, so we cannot do any pharmacokinetic calculations. However, it does have some moderate antiviral effects against Epstein-Barr virus, which my pharmacokinetic calculations show (see table below), so tenofovir might have some use in EBV-associated ME/CFS, as well as enterovirus-associated ME/CFS.
Here is a screenshot for the calculated Potency Factor for Epivir and tenofovir against various viruses (hepatitis B virus, HIV, and Epstein-Barr virus):
As you can see, tenofovir is highly potent against HIV, with a Potency Factor of over 20 thousand.
For
ribavirin, this drug does not have strong antiviral effects, as the table below demonstrates:
The reason ribavirin's Potency Factors are low in spite of being sold as an antiviral is likely because ribavirin fights viruses by various immunomodulatory mechanisms, in addition to its direct antiviral effects.
Immunomodulatory mechanisms are not accounted for in the pharmacokinetic Potency Factor calculation, a calculation which is based on in vitro data. In general there is no way to test or measure immunomodulatory effects in vitro, because these effects act on the entire immune system, and you cannot mimic the immune system in vitro in a cell line.
So my pharmacokinetic calculations can only measure the direct antiviral effect of a substance, but they cannot measure any immune boosting effects the substance may have which will also fight the viral infection.
Ribavirin is problematic in long-term use, due to risk of serious side effects, so is not much use in ME/CFS linked to chronic enterovirus.
Also Hip, on another topic, what is your thought on or even better, GS 441524 for enteroviral persistence?
Remdesivir might have some effects against the enteroviruses found in ME/CFS, but its extraordinarily high price would preclude it as an ME/CFS treatment, unless a short course of the drug had permanently benefits. Some antiviral/immunomodulatory drugs like tenofovir seem to permanently improve ME/CFS, but with other drugs, the benefits disappear when you stop taking them.
At around $400 per dose, only a multi-millionaire could afford to take this drug daily on a long-term basis.
