Innovation Pharmaceuticals Inc (IPIX)

[PJ007]

Informative post by airplaneguy

*Brilacidin versus Small Pox*

First we define Brilacidin, which is a Definsin Mimetic meaning it mimics definsins
Bio-computational designed Brilacidin is a synthetic non-peptide defensin mimic drug that destabilizes the viral membrane by its amphipathic & hydrophobic nature, and its immunomodulatory property influence.

Defensins : are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune signalling activities, or both. They are variously active against bacteria, fungi and many enveloped and nonenveloped viruses. (enveloped or Alpha viruses are the worst) Brilacidin destroys the outer membrane in a virus or bacteria.
Mimetic : It Mimics or Relating to, characteristic of, or exhibiting mimicry.

LL-37 : HDP Human Defensin Protein
The antimicrobial peptide LL-37 is the only known member of the cathelicidin family of peptides expressed in humans. LL-37 is a multifunctional host defense molecule essential for normal immune responses to infection and tissue injury.
LL-16 : Antimicrobal Peptide LL-16 (a 16 residue truncastion of human cathelicidin LL37

Comparing Brilacidin to HDP - LL-37 and LL16
If we compare Brilacidin to the lipopeptidic antibiotic daptomycin, a Ca2+-dependent anionic lipopeptide with activity against Gram-positive bacteria, and the antimicrobial peptide LL16 (a 16-residue truncation of human cathelicidin LL37). LL37 is an alpha-helical antimicrobial peptide known to exert antibacterial activity via membrane permeabilization. (i.e. Think salt concentration and membrane permeability) We found that Brilacidin treatment causes levels of membrane depolarization in Staphylococcus aureus similar to those of daptomycin, suggesting that membrane activity is the primary initial target.

Transcriptional profiling shows that Brilacidin, daptomycin, and LL16 treatments cause a significant induction of the NsaSR (nisin sensitivity-associated) two-component system as well as the cell wall stress-responsive VraSR and WalKR two-component system regulons.

What does this mean in terms Brilacidin and the efficacy against small pox?

It has been demonstrated that HDP are an important component of innate immunity against Virola Major or small pox virus. Studies have determined that the cathelicidin LL-37 inactivates virola major ( Small Pox = Virola Major) by a “carpet-based mechanism”, it removes the outer membrane of the virus.
It was shown that HDP, including LL-37, were efficient at removing the outer membrane and that they might also, without the requirement for membrane removal, alter the exposure of antigens allowing susceptibility to neutralizing antibody. This suggests that the peptides may simultaneously induce direct killing by the carpet-based mechanism, but could also reveal sequestered antigens for antibody binding, and subsequent clearance by the adaptive immune response.