Innovation Pharmaceuticals Inc (IPIX)

[farrell90]

Phosphlipidosis requires intracelllular vesicle {also called lysosomes} formation to become manifest.The vesicles are the hallmark of both phosphlipidosis as well as possible drug resistance.The vesicles normally develop as a part of the manufacture and release of new viruses.

Just to review, Covid, like any virus circulates through the body and infects cells which takes several steps :

1. the viruses attach to cell walls or cell wall receptors ie ACE receptors

2.the viruses enter the cells

3.the viral m protein engages the cellular organelles, Golgi ribosomes etc to manufacture new viruses

4 The mature viruses are encased in vesicles {lysosomes] which attach to the inside of the cell wall and are released into the extracellular spaces where they can infect other cells and complete the process.

"Drug-induced phospholipidosis is a lysosomal storage disorder characterized by an intracellular excessive accumulation of phospholipids {in vesicles}. Its cellular mechanism is still not well understood, but it is known that cationic amphiphilic drugs can induce it. These drugs have a hydrophilic amine head group that can be protonated in the endolysosomal compartment...By compensating the negative surface charge, cationic enzymes are released from the surface of vesicles and proteolytically degraded, triggering a progressive lipid storage and the formation of inactive lamellar bodies...Drug-induced phospholipidosis (DIPL) is caused by long-term treatment of animals and humans with cationic amphiphilic drugs (CADs) leading to an intracellular accumulation of phospholipids in kidney, liver, lung, brain, cornea and other organs."

https://www.degruyter.com/document/doi/10.1515/hsz-2019-0270/html

Reasons it is unlikely Brilacidin could be associated with phosphlipidosis

1 The primary mechanism of action of Brilacidin is killing the virus in the extracellular space.

2. The secondary mechanism of action is Brilacidin prevents viral attachment to the cells.

3 Brilacidin prevents the virus from entering the cell by 2 mechanisms

4. Since it does not enter the cell the phospholipid vesicals or lysosomes will not be formed.

5.A computer modeling study suggested Brilacidin prevents expression of the viral M protein which again would prevent intracellular lysosome formation

6. Phosphlipidosis and Brilacidin drug resistance is prevented by 3 Brilacidin mechanisms of action

7.Phospholipidosis is associated with long term drug usage. Since Brilacidin will only be used 5 days at the most it is not likely to develop a lysosomal storage disorder in a short time period.

"brilacidin exhibits robust inhibition of SARS-CoV-2 in Vero cells and Calu-3 cells, and in two strains of the virus. Likely to function as a viral entry inhibitor [73,74,75], the proposed mechanism of action for brilacidin includes affecting the integrity of the viral membrane and interfering with viral entry."

https://www.mdpi.com/1999-4915/13/2/271/htm

Remember inherited lysosomal storage disorders in children take years or decades to become manifest.The best known example is Tay-Sachs disease where the young children are normal but they deteriorate with age.

https://www.degruyter.com/document/doi/10.1515/hsz-2019-0270/html

GLTA, Farrell