Innovation Pharmaceuticals Inc (IPIX)

[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.