Innovation Pharmaceuticals Inc (IPIX)

[PlentyParanoid]

I did some reading this week and learned mostly unhelpful things. Farrell and others have covered most that follows before, but it is still worth repeating.

How does SARS-CoV-2 virus enter human cells?
It is known that cell entry by the coronavirus requires the binding of the S1 region of the virus spike (S) protein to the cell surface receptor followed by the fusion of the viral and cellular membranes mediated by the S2 subunit of S protein. This process requires S protein priming by host cell proteases, which entails S protein cleavage at the boundary of S1 and S2 proteins or within the S2 subunit. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as cell entry receptor and transmembrane serine protease 2 (TMPRSS2) and/or the endosomal cysteine proteases cathepsin B and L (CatB/L) for S protein priming. It is thought that TMPRSS2 activity is essential for viral spread. Alveolar type 2 cells in lungs highly express both ACE2 and TMPRSS2.

The above is probably no news for most people around here. Well, here comes the distressing part of my findings. It turns out that SARS-CoV-2 can utilized some other receptors for entry, although using ACE2 remains the most efficient entry method. Among alternate entries are CD209 and CD209L. CD209L is expressed in lung and kidney epithelial cells and in endothelial cells of small and medium-sized vessels. Then there seems to be cell entry methods utilizing Neuropilin receptors and CD147/Basigin receptor. Note to male readers: CD147 is important in spermatogenesis and its presence in entry point list may explain why SARS-CoV-2 has been found in testes.

I occurred to me that any single inhibitor or receptor blocker needs be to amazingly talented if it intends to be successful. I would say that preventing SARS-CoV-2 cell entry will require quite a cocktail of antivirals. And I am talking only about cell entry. What happens after entry is another story.

It might be better if we had a treatment that would outright kill the virus instead of trying to inhibit or block. Has anybody around here heard of this kind of drug? It would be helpful if it is already proven to be safe in humans.

For additional reading:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407648/