Replies to post #283566 on Innovation Pharmaceuticals Inc (IPIX)

[TheDane]

POST OF THE MONTH!!! Nice job.condensing this for the common man, Farrell!

[Jhawker]

Awesome post! Please sticky

[zandant]

"Leo should be applauded for putting together this professional review."

It took the guy a month just to get his phone message system in his virtual office set up. I highly doubt he was responsible for putting together this "professional review." More likely put together by the LW staff.

[rrr1]

I just grabbed a position today. So I know I need to do some reading but Quick Q I know they have some Phase trials done are they completed on Phase 2 already I see you mention Phase 3 at the bottom of this fine post.

[TheDane]

Covid-19 and Leo’s impressive sieving of opportunity getting Brilicidin into the lab for testing - the mark of a leader! - is generating discussion of IPIX’s science. That’s terrific and will benefit though who might be new shareholders who thought this was only a “”CV Play.” Farrell, your post boils down the essence of what’s at stake, the science and what it means to IPIX and it’s shareholders and, hopefully, victims of the hideous disease.

Reprint!

“Very impressive review of Brilacin and its potential anti viral and specifically its anti coronal virus effects. It is easy to see why researchers want to urgently test Brilacidin in hopes of stemming the epidemic.

Most reports show the fatalities are due to respiratory failure which would include direct viral pneumonia plus secondary bacterial infection.In addition reports note severe pulmonary inflammation and fibrosis complicating the infection and resulting in respiratory failure and requiring mechanical ventilation.

Brilacidin's antibiotic, anti inflammatory and now possible antiviral effects seem to be ideal to combat the pulmonary effects of coronavirus.

The mechanism of it viral action seems to be the same as its bacterial mechanism of action. Brilacidin attaches to the bacterial cell wall and the viral protein coat which results in their lysis and subsequent destruction.

Brilacidin's anti inflammatory effects would help combat the excessive inflammation and scarring which results in blockage of the air sacs [aveoli] and small airways[bronchi] and ends in respiratory failure.

For IPIX this is a no risk venture. At a minimum Brilacidin is going to receive intensive and expensive study. At best it will be shown to be an important therapeutic to combat the corona virus epidemic.

My guess is the optimal therapy will include an antiviral plus an agent or agents {which could be Brilacidin} which would have an anti inflammatory and antibiotic effect. Brilacidin could be given as an IV dose early in the disease to prevent respiratory failure. As I recall its biologic effect is a number of days. Then it could be repeated later if needed.

Leo should be applauded for putting together this professional review. I have been trying to research these items all week and have only had partial success.

Another guess is the labs will complete their in vitro Brilacidin studies quickly. If they confirm Polymedix's early preclincal studies showing Brilacidin is effective against Coronavirus we will see a greatly accelerated FDA phase 3 study which will be done on a worldwide emergent basis at no cost to IPIX.

All the above is in my opinion only. It is an exciting time for IPIX and Brilacidin. We should know in a few weeks how things work out.

GLTA Farrell

[KMBJN]

Thanks for the nice recap. Am wondering if you can say some more about this:

"The mechanism of it viral action seems to be the same as its bacterial mechanism of action. Brilacidin attaches to the bacterial cell wall and the viral protein coat which results in their lysis and subsequent destruction."

and this:

"Polymedix's early preclincal studies showing Brilacidin is effective against Coronavirus"

Would you mind sharing any sources or papers about brilacidin's potential anti-viral properties or mechanism of action? I have seen a few things about HDPs against viruses. It's pretty complicated and depends on which defensin and which virus one is talking about. A lot of the mechanisms depend on the HDPs being lectins that can bind to viral entry proteins (CoV S protein, HIV gp120, HSV gD?), and I don't think brilacidin can serve the same function.

I guess if it is just a cationic molecule like brilacidin puncturing the enveloped virus lipid bilayer, then brilacidin could work, and we should find out pretty quickly.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842434/

Defensin perturbation of lipid bilayers is dependent upon their composition. It is favored by negatively charged phospholipids; whereas, neutral bilayers are largely inert to defensin 65; 75. The lipid content of viral envelopes is dependent upon the subcellular location and membrane microdomains from which they bud and likely varies among viral families 76. If direct membrane perturbation contributes to the antiviral effect of defensins, then differences in the lipid composition of the envelope may in part explain the differential susceptibility of viruses to defensins.

Does SARS-CoV-2 have a negatively charged lipid bilayer that is susceptible to a cationic killer like brilacidin (disrupting bacterial negatively charged outer membranes)?

The one nature paper talks about a monkey theta defensin being immunomodulatory in a SARS model:

https://www.nature.com/articles/nrd.2015.37

Which type of HDP does brilacidin most closely mimic?

This paper has a nice section talking about defensins potential role against coronaviruses:

https://onlinelibrary.wiley.com/doi/10.1002/jmv.25685

2.9 Defensins

Defensins are a family of endogenous antibiotic peptide molecules, which widely exist in human, animals, and plants, and are important for the host's innate defense system. Defensins have broad-spectrum antimicrobial activities. In vitro inhibition experiments show that defensins have killing effects on bacteria, fungi, mycoplasma, chlamydia, spirochetes, tumor cells, and viruses.60, 61

Defensins of human and rabbit neutrophils are mainly found in the eosinophilic granules of neutrophils. They are small molecular cationic polypeptides composed of 29 to 34 amino acid residues, with a relative molecular weight of 3500 to 4000 dolt and three intramolecular disulfide bonds. They are main components of the neutrophils independent of oxygen sterilization.62, 63 Human a-defensin HNP-1 inactivates herpes simplex virus type I and type II (HSV-1 and HSV-2), cytomegalovirus (CMV), VSV, and IAV.64, 65 Purified defensins of guinea pigs, rabbits, and rats have weak anti-HIV-1 activity.66, 67

However, some studies showed that purified human neutrophil defensin (HNP1-3) and rabbit neutrophil defensins (RNP1–5) could neither inhibit nor kill SARS-CoV.68, 69

Trying to figure out if brilacidin potentially has anything useful against coronavirus, and I still don't understand all the potential mechanism(s) by which it could be helpful.