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Fluoxetine (Prozac) as Enterovirus B Replication Inhibitor

sometexan84

sometexan84

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Hip

Hip

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Some years ago, Dr Chia tried fluoxetine (Prozac) for his enterovirus ME/CFS patients, but I have heard not any reports of success.

On this forum, @JES tried Prozac as an enterovirus antiviral, but did not see benefits.


According to some calculations I did, when you take fluoxetine, the blood levels of fluoxetine achieved are not high enough to have any significant antiviral effect.

In the brain though, there may be some mild antiviral effects, as over a few months of oral dosing, fluoxetine accumulates in the brain tissues to high levels, and there have been some published case studies of fluoxetine being use to treat acute enterovirus brain infections with success.

In ME/CFS though we are not dealing with acute enterovirus infection, but a chronic non-cytolytic enterovirus infection, which is a different mode of infection (non-cytolytic infections live inside human cells).



I compiled a list of drugs and supplements which are antiviral in vitro for enterovirus here.

Unfortunately, according to calculations I performed, none of these will actually have any significant antiviral effect in vivo, because when you take these substances, sufficiently high blood levels cannot be achieved.

In vitro studies often use high concentrations of the substance, but in vivo it is often not possible to match those high concentrations in the blood, so for practical purposes, these substances in my list are not effective antivirals in vivo, unfortunately.

I was really hoping to find some supplement or off-label drug that would work for enterovirus in vivo, but alas I could not really identify one.


The only substances that my calculations suggest could have some mild antiviral effects for enterovirus are: black soybean (Glycine max) at high doses, but when I tried this, it increased brain fog and mental vagueness, so I stopped.

The drug Arbidol might be effective for enterovirus, and one person on this forum tried it, seeing perhaps some mild benefits.

Low-dose oral interferon might also be worth trying for enterovirus; one case of full remission from ME/CFS from low-dose oral interferon is detailed in this thread. I have not yet tried this properly.
 
sometexan84

sometexan84

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1,235
As far as the in vivo blood level activity calculations, the article seems to address it.

That whole paragraph that starts with "The in vivo efficacy of fluoxetine toward enterovirus infections has until now been relatively poorly studied"

Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner

"The plasma concentration of fluoxetine ranges from 91 to 300 ng/mL after 30 days of dosing 40 mg/day"

"The metabolite norfluoxetine, which also shows antiviral activity,(33) reaches a plasma concentration from 72 to 258 ng/mL. The slow elimination of fluoxetine together with the metabolite norfluoxetine should reach a sufficient plasma concentration that corresponds with the EC50 in cell culture (∼1 μM, which corresponds to ∼150 ng/mL)"

Just to be clear, they say it's a replication inhibitor. It inhibits the 2C protein, which is necessary for enterovirus B to replicate.

Also, they describe in tons of detail how it's just the (S)-Fluoxetine portion that has the antiviral effect. And so you wouldn't have to take full Prozac dose and get all the side effects.

"(S)-Fluoxetine Inhibits CVB3 Replication by Binding to the Nonstructural Protein 2C"
 
Hip

Hip

Senior Member
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17,858
sometexan84 said:
"The metabolite norfluoxetine, which also shows antiviral activity,(33) reaches a plasma concentration from 72 to 258 ng/mL. The slow elimination of fluoxetine together with the metabolite norfluoxetine should reach a sufficient plasma concentration that corresponds with the EC50 in cell culture (∼1 μM, which corresponds to ∼150 ng/mL)"
Click to expand...

One thing they do not seem to have taken into account is the high plasma protein binding of fluoxetine, which is 95%. This means 95% of fluoxetine binds to proteins in the blood, and once bound it becomes inactive (as an antiviral). It's only the free unbound fluoxetine which is still active.
 
K

knackers323

Senior Member
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sometexan84 said:
Haven't heard anything about it
Click to expand...

ive tested positive to enterovirus' and get a large improvement from paroxetine that i dont get with any other drug in the same class.
i have spoken to a few others that have also noticed the same thing, so there seems like there might be another factor besides the SSRI/depression effects. i wonder if an effect on enterovirus' might be it
 
JES

JES

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1,322
knackers323 said:
ive tested positive to enterovirus' and get a large improvement from paroxetine that i dont get with any other drug in the same class.
i have spoken to a few others that have also noticed the same thing, so there seems like there might be another factor besides the SSRI/depression effects. i wonder if an effect on enterovirus' might be it
Click to expand...

Paroxetine is not showing the same antiviral effects, at least according to this study:

On the basis of the idea that fluoxetine appears to act on a viral protein and not on a cellular host factor, we deem it unlikely that other selective serotonin reuptake inhibitors would exhibit an antiviral effect, unless they are similar in structure to fluoxetine. In fact, we did not observe any inhibitory activity of three other selective serotonin reuptake inhibitors, i.e., citalopram (EC50, >160 μM; CC50, >160 μM), paroxetine (EC50, >22.18 μM; CC50, 22.18 ± 0.41 μM), and sertraline (EC50, >17.12 μM; CC50, 17.12 ± 1.17 μM), on CVB3, which is further evidence that the antiviral effect of fluoxetine relates to its specific pharmacophore interacting with 2C and that the antiviral effect is unrelated to serotonin uptake.
Click to expand...

Anyway, it could well be some other factor that causes the improvement with paroxetine in specific. Ron Davis' son for example has recently gone back to writing with low-dose Abilify and some other treatments, they don't understand why. I tried paroxetine as well several years ago and it didn't do anything special for me. I still get benefits from SSRI's for the first 24-48 hours, then the benefit wears off and never returns. Inexplicable.
 
Pyrrhus

Pyrrhus

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sometexan84 said:
July 15, 2019 - Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner
Click to expand...

New paper from the same author (Lisa Bauer):

Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex (Hurdliss et al., 2022)
https://doi.org/10.1126/sciadv.abj7615


And the two older papers:

Fluoxetine is a potent inhibitor of coxsackievirus replication (Zuo et al., 2012)
https://doi.org/10.1128/AAC.00983-12

Selective serotonin reuptake inhibitor fluoxetine inhibits replication of human enteroviruses B and D by targeting viral protein 2C (Ulferts et al., 2013)
https://doi.org/10.1128/AAC.02084-12
 
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