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Re: petemantx post# 315244

Monday, 07/27/2020 4:18:48 PM

Monday, July 27, 2020 4:18:48 PM

Post# of 405226
No, they tested preclinical targets too, including brilacidin:

Towards this end, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. We report the identification of 100 molecules that inhibit viral replication, including 21 known drugs that exhibit dose response relationships. Of these, thirteen were found to harbor effective concentrations likely commensurate with achievable therapeutic doses in patients ...

..

Here,
we describe a high-throughput reprofiling screen using the ReFRAME
(Repurposing, Focused Rescue, and Accelerated Medchem) drug
library, a comprehensive open-access library of ~12,000 that have been
either FDA-approved or registered outside the US, entered clinical trials,
or undergone significant pre-clinical characterization14, to identify
existing drugs that harbor antiviral activity against SARS-CoV-2 in a
cell-based assay14,15.



and it looks like brilacidin was in the database of 12,000 compounds:

https://reframedb.org/search?query=brilacidin&type=string

Maybe it was a difference in methods such as SARS2 isolate or MOI used or hours post infection?

Brilacidin in RBL hands inhibited SARS2 by ~50% at 5 uM in VERO cells 16 hours post infection:



From the Nature study:

Specifically, the potential antiviral activity of 11,987 compounds
against SARS-CoV-2 was assessed in Vero E6 cells. The assay,
conducted at a final compound concentration of 5 µM was designed to
capture multicycle replication, based upon low viral input (MOI = 0.01)
and an extended endpoint measurement (72 hours post-infection).


...

Approximately 300 compounds were identified for validation
studies based on criteria outlined in Materials & Methods (also see
supplementary Discussion). We assessed the activity of selected hits
at 2.5 and 1 µM, in contrast to the 5 µM concentrations employed in the
original screen, using an orthogonal assay readout. Specifically, Vero E6
cells treated with selected compounds were challenged with another
SARS-CoV-2 isolate (SARS-CoV-2 USA-WA1/2020), and viral infection
directly quantified through immunostaining





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