A few more notes on the recent published paper,
BIT225 treatment of SARS-CoV-2 in K18-hACE2 mice.
But first, you may recall a few days ago that a link to a paper was posted above explaining why mice model trials of drugs do not necessraily translate into the same results in humans. The central claim in that paper, and mostly undisputed in research, is that certain cells in mice that are suseptible to affect by the drug being administered in a mouse trial, are not necessarily affected in the dsame way, if at all, in humans. The result being that the drug in question does not work in humans like it does in mice. This is mostly because certain cells in both species, even though mostly identical and play similiar or identical roles in both mice and man, behave differently in each because of the complex relationships between those cells and others, where in one species a certain cell might be selected for/activated, whereas the equivalent cell in the other speices is not. Such relationships and behaviour of the same cells between humans and mice therefore cause different outcomes in trials.
This of course is what we are waiting to see with the forthcoming C19 human trials, but I'm banking on these human trial results replicating much the same as occurred in mice for the following reasons.
Mice and men both suffer much the same way in Covid, where the cytokine storm can aggressively develop. Even though in humans the response greatly varies when infected by SARS2, with some hardly being affected at all while others totally succumbing to it, this should not be seen as relevant in our expectations of our forthcoming human trial results. In other words, the difference in outcomes in humans, in my view, has no relevance to the statistial high level of disease in all of the vehicle mice. The fact that all mice succumbed to C19, as opposed to humans in general, is because our mice were genetically enhanced with ACE2 receptors. As such, they are all more likely to be predisposed to succumbing to C19 whereas humans in the natural world do not have such enhanced ACE2, resulting in C19 being able to run its natural course, with various degrees of disease development.
The mice all suffered from high levels of IL-6, triggered by SARS2, and one of the the principle agents responsible for the cytokine storm in both humans and our mice.
The fact that BIT225 demonstrated in the
in vitro segment of the trial a significant reduction in ion channel activity:
"
The ion channel activity of SARS-CoV-2 E protein was measured by two-electrode voltageclamp in xenopus oocytes. Oocytes injected with cRNA encoding the E protein showed significantly higher depolarization of the resting membrane potential (-19.5 ± 3.3 mV, SEM, n = 5)
as compared to control, uninjected, oocytes (-53.3 ± 1.8 mV, SEM, n = 5; Fig 1A). In addition, the current-voltage curves show the injected oocytes had greater conductance than the uninjected oocytes, confirming E protein ion channel activity (Fig 1B).... These results indicate selective inhibition of E protein ion channel activity by BIT225 and the ability of BIT225 to fully suppress E protein ion channel current."It is very likely, if not demonstrated, that this reduction in ion channel activity in vitro is also the same reason why our BIT225 treated mice were able to continue to thrive as opposed to the vehicel mice that all succumbed to C-19.
The question outstanding then is will BIT225 reduce ion channeling in humans AND have the same reduction in the IL-6 proteins that lead to the cytokine storm? (IL-6 was highly elevated on the vehicle mice, as it is in humans who have advanced C-19 disease progression).
The mode of action of BIT225 thus far
in vitro and in mice is its ability to shut down the necessary paythway of ion movement through E which plays a crucial role in disease development. It seems to me that this reaction in the ion channel gateway is a chemical operation constant between the electro-ion channels of E wherever it is found.
Whether or not the other viroporins within SARS2 - Orf3a, ORF7b and ORF10 - can circumvent the necessray ion chanelling to resume diesease development is yet to be seen, but from what I've read in other papers to do mostly with viroporin inhibitors, I'm not expecting SARS2 in humans to escape BIT225's mode of action.
I wouldn't be surprise though if further phase 2 trials are instigated.
End.
On another note and to dampen any excitement, Biotron's recent letter to shareholders suggesting "headline news," etc, may be just a ploy by MM to create a pump so she is able to cash in on her expriing options next month......
. That of course is a very cynical view of it all.
(20min delay)