MND PK PD data and why it influences the upcoming Covid-19 trial

Monepantel is an positive allosteric modulator, which means it is a substance that binds to a receptor to increase efficacy.

The Ace 2 receptor is the initial contact between Covid 19 and your body in the nose.

Dutta et al in their study " Allosteric site of Ace-2 as a drug target for Covid-19 2021"states " the ACE-2 interaction may be targeted by anti viral drugs. Allosteric modulation of Ace-2 may offer a promising approach, it may lead allostericInhibition of interaction between Ace-2 and SARS-CoV-2 ".

This is supported by a study by Hochuli 2022 " Allosteric binders of Ace-2 are promising anti SARS-CoV-2 agents " Interestingly that positive Allosteric modulators are positive AMPA receptors a type of glutamate which mediates most fast synaptic neurotransmitters in the central nervous system . An important MND link.

In Nickbakts study 2020 " How does the Covid-19 cause seizures and epilepsy in patients ? The potential mechanisms". They state " these cytokines increased the entry of calcium through AMPA and NMDA receptors increasing neuronal hyper excitability and death".

A study " Positive Allosteric Modulators that target NMDA receptors rectify loss of GRIN variants associated with neurological and neuropsychiatric disorders " Tang et al 2020 .

So the assumption is Monepantel being deemed as safe may have possible in roads in a form of treatment and prevention.Let's look deeper.

Stuchilikova in 2015 in their study " Monepantel induces hepatic cytochromes P450 in sheep invivo

and invitro " indentified results show significantly increased all cytochromes related activities and CYP3A4 mRNA in sheep"

Now it has been noted that hyperinflammatory states may trigger significant derangements in hepatic cytochrome P450 metabolic machinery.

In a study " The role of cytochrome P450 enzymes in Covid-19 pathogenesis and therapy " Wang et al 2022. Wang found " CYP3A4 activity was suppressed in primary hepatocytes infected with adenovirus " and " CYP450 is under expressed in Covid-19"

Studies state myocarditis is a factor in long Covid-19.But why is that so and what has Monepantel got to do with that.

In " Regulation of Ace 2 in cardiac myocytes and Fibrolasts " Tallant 2008 states " this data suggests myocytes maybe a source of Ace 2 in the heart" also " the discovery of cytochrome P450 in cardiomyocytes may have in pharmacotherapy".As you can see Monepantel affects increases P450. What other interactions are at play.

In Clins study 2020 " What about Covid-19 and the arachidonic acid pathway", Clin states " arachidonic acid acts as an endogenous anti viral compound and a reduction of arachidonic acid makes humans more prevalent to Covid-19" , the author also states " the major role for P450 dependant mechanism is via arachidonic acid metabolism".

Mete et al 2021 in their study " Effects of anti viral drug therapy on dynamic Thiol/Sulphide homeostasis and nitric oxide levels in Covid-19 patients" state " strongly suggest that Thiol/Disulfide homeostasis is disturbed in patients with Covid-19" also that " reduced and oxidised Thiol levels play a critical role in pathogenesis of Covid-19".

Ok you say what's the link with Monepantel.Schmidt et al 2021 states in their study " Changes in serum Thiol-Disulphide homeostasis in sheep with Gastrointestinal nematodes " that " Thiol-Disulphide balance is impaired in lambs infected with gastrointestinal nematodes"What does Monepantel do with sheep infected with nematodes ? Cures them .

So lots of highly technical data enclosed. For me to explain it all would take all day and most would switch off ( understandable) but these are my views on why Monepantel works in humans.

The data from WEHI / 360 Labs and Leiden all point to success.

I am happy to field questions !Proof is in the pudding.

Anyway as usual " you heard it here first " kpax et al 2023.

Hot Copper is a brilliant forum with brilliant minds why doesn't PAA make use of it. Long term posters can't argue with that because they post long term.Today, Pharmaust just hit the HC homepage top posts.

Also why hasn't PAA used Facebook on its website. Imagine your dog has cancer you type " lymphoma B dog cancer " and straight away you are linked to the PAA trial page on their website. Costs $12.07 for one thousand clicks. Costs nothing to set up. If you agree email Anusha.

Chat soon

Kpax