Replies to post #283708 on Innovation Pharmaceuticals Inc (IPIX)

[MackG]

farrell90, thanks for taking the time to share all of this important background information with us. It certainly bolsters my confidence in understanding the origins of the research behind Brilacidin and the facts-based hope we have in this amazing drug compound to alleviate suffering in so many indications. I pray that it proves to be an effective therapy in combating the C-19 virus.

[rmzport]

farrell..Thank you! Really nice dig!! "Brilacidin already has demonstrated broad and robust antibacterial,
anti-inflammatory and immunomodulatory properties in multiple FDA clinical
trials. Pre-clinical research also supports Brilacidin’s antiviral properties
based on work by conducted by Dr. William DeGrado (UCSF) and Dr. Richard Scott
(Fox Chase). "

[KMBJN]

Correct, I haven't seen any information about HPDms as antivirals or their presumed MOA from Polymedix or published, (which is why I was asking).

Regarding direct activity of brilacidin or other HDPms against viruses, I believe it would have to be against the lipid bilayer (only if it is negatively charged like bacterial outer membrane). Being non peptide, I don't think it would interact with viral receptor-binding glycopeptides (like gp120, S, or gD) the same wasy as HDPs.

I also had gathered that brilacidin was most similar to magnainin, which is not closely related to any human defensin protein in particular. The monkey SARS study used a theta-defensin, again not similar to brilacidin (and theta defensins don't exist in humans, but could be helpful as anti-inflammatory / immunomodulatory in humans).

BTW, there is information updated today to include 22 pages (from 9 or 10) on brilacidin and COVID-19.

https://www.ipharminc.com/s/IPIX-Brilacidin-Defensin-Mimetics-COVID-19-Overview-March-1-2020-update.pdf

I can't find this quote on the blog:

Pre-clinical research also supports Brilacidin’s antiviral properties based on work by conducted by Dr. William DeGrado (UCSF) and Dr. Richard Scott (Fox Chase).

[EDIT: nevermind, found it on the 2/18/20 blog, not the 2/28/20 one]

Am curious, who is writing this blog as IPIX seems to consist mostly of Leo Ehrlich and not too many other employees.

Likewise, how is the company planning to do this without relevant expertise?

The Company is making plans potentially to test additional defensin-mimetic compounds (synthetic analogs similar to Brilacidin) that might be tailored to exhibit enhanced antiviral activity.

Thanks for the magainin peptide analog paper against HSV. Unfortunately, I'm not sure how much carries over to synthetic non-peptide small molecules (poly-arylamides) like brilacidin. Peptides with arginine, lysine, and cystine richness did better at inactivating HSV. Hopefully it's just being a small cationic molecule that is needed. And hopefully SARS-CoV-2 has negatively charged lipid bilayer envelope that can be destroyed by brilacidin's cationic "spears." We should find out before too long!


Then there is the whole issue of how is brilacidin immunomodulatory and anti-inflammatory? We do know that it inhibits PDE3 and PDE4, but there must be more to the story. I think I recall reading that defensins block the innate immune inflammatory response (via TLRs) triggered by bacterial wall components like LPS and LTA. Again, is it as simple as defensins or brilacidin binding to these components to block inflammation?

Glad that brilacidin is such a versatile, potentially valuable molecule that is being tested as anti-viral, and appreciate you sharing your expertise.