"In short, ABET distrupt viral replication...But more importantly, it also inhibits expression of Angiotensing Convetting Enzyme 2 (AcE2), the receptor used by the virus to get entry into the cells. In order for the virus to be effective, it 1st has to get entery into cells, & then use to cell DNA macinaty to replicate & reproduce! it seems that ABET inhibit both of these princesses!"

I have seen zero evidence supporting that ABET disrupts viral replication or that ABET disrupts the interaction of viral protein E with BRD2/BRD4. As far as I can tell, these are both unproven hypotheses. But that is where science starts. The BioRxiv paper highlights several potential druggable interactions. However, I see zero data in that paper that tested any of these drugs, including ABET; only hypothesized their potential. I'd be happy if someone proves me wrong, but I'm just not seeing it in the paper, and I don't quite see how Resverlogix was justified in making their explicit statement that "Apabetalone was shown to disrupt this interaction."

I reached out to some of the authors on Twitter. I asked "If both E & BET inhibitors block BRD2/BRD4 binding to acetylated histones, then what is the hypothesized mechanism for how BET inhibitors amerliorates the viral infection process? Is it the change in host gene expression? If so, how does one reconcile that both BET inhibitors & E binding are predicted to modulate host gene expression? Is it specifically the binding of E to BRD2 and/or BRD4, which BET inhibitors may compete with and prevent? Thx in advance."

Author James Fraser replied "Correct, it is quite possible that drugging some of these interacting proteins (e.g. BRD2/4) might HELP the virus. The next set of cell culture experiments (done at @MountSinaiNYC and @institutpasteur)  will help prioritize those likely to tilt things in the right direction."

So sounds like they still need to test apabetalone.

As for the ability of apabetalone to lower ACE2 and whether ACE2 lowering makes a lick of difference........I posted earlier that "apabetalone has been previously shown to reduce expression of ACE2. However, the only manuscript (after a quick search) that I could find was this one and it was only a modest decrease (30%, -1.3-fold) and it was observed in human whole blood treated ex-vivo for 24 hours. I would feel more confident in this proposed mechanism with some additional confirmatory data showing reduced ACE2 mRNA, total protein and cell surface protein expression in other experiments and model systems."

1) A modest 30% reduction might not do much. 2) This is mRNA change, not protein; they don't always correlate. 3) Says nothing about cell surface expression of ACE2. 4) Still no evidence that I know of that modulation of ACE2 expression has any impact on the viral infection/replication process. Lots of hypotheses, nothing proven.

Sorry to poke holes in your princess (process) bubble. 

BDAZ