Innovation Pharmaceuticals Inc (IPIX)

[KMBJN]

I am a believer in trying low cost and safe drugs like HCQ in combination with zinc. Not sure about the Z-pak though, if that would be necessary.

In any event, I found this German study interesting, trying to figure out how chloroquine and hydroxychlorquine work:

https://medicalxpress.com/news/2020-07-malaria-drug-chloroquine-inhibit-sars-cov-.html

https://www.nature.com/articles/s41586-020-2575-3

There are two ways for SARS2 to enter cells, via ACE2 (after cleavage of spike protein by both furin and TMPRSS2) and direct fusion with cellular membrane, and via endosomes (low pH and cathepsin L dependent, apparently also needing ACE2, but independent of TMPRSS2). It was thought that CQ and HCQ raise endosome pH such that virus can't escape into cells (blocking cathepsin L).

Reviews of SARS2 viral entry:
https://www.pnas.org/content/117/21/11727
https://www.sciencedirect.com/science/article/pii/S0300908420301280

Interesting here that glycopeptide antibiotics block cathepsin L and block CoV viral entry (and I think azithromycin is a macrolide form of one? so may be synergistic in blocking cathepsin L):

https://pubmed.ncbi.nlm.nih.gov/26953343/

The German paper claims chloroquine works in vero cells but not lung epithelial cell lines to inhibit SARS2, because those human lung cells had very little cathepsin L, but more TMPRSS2. They go on to claim (H)CQ won't work in humans to protect lung cells because of this.

So, two things.
(1) I'm glad we got confirmation in human lung cell lines that brilacidin inhibits SARS2 there in addition to Vero cells - and appears to do so at safe and previously achieved concentrations in humans.
(2) It may be that multiple SARS2 cellular uptake antivirals would be helpful: (H)CQ or other cathepsin L blocker to inhibit endosomal uptake, camostat to block TMPRSS2, and perhaps brilacidin to either kill virus externally or perhaps prevent fusion via ACE2 entry pathway somehow.

Looking forward to reading the results exploring how brilacidin works to inhibit human lung cell infection with SARS2.