Bril and Intra Cellular Impact on Viral Replicatio
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Posted On: 11/08/2021 8:10:47 AM
Bril and Intra Cellular Impact on Viral Replication
""While brilacidin’s mechanism of action appears primarily to be extracellular, it may also impact intracellular viral replication and is planned to be researched further. Supportive of this, an in silico quantum mechanical molecular screening study of 11,522 compounds identified brilacidin as a potential inhibitor of SARS-CoV-2 based on the potential of its physico-chemical properties to interfere with the intracellular replication of SARS-CoV-2’s main protease (Mpro).90
The high CC50 (a measure of cytotoxicity) and low IC50 (a measure of potency) values observed for brilacidin in Calu-3 cells—yielding a Selectivity Index (SI) for brilacidin of 426 (CC50=241μM/IC50=0.5 65μM)—strongly support brilacidin’s treatment potential to achieve positive antiviral outcomes in humans. A vast majority of other drugs being evaluated as potential COVID-19 treatments, including repurposed drugs, have SIs that are much lower than that achieved by brilacidin,91 with most drugs failing to show anti-SARS-CoV-2 potency in the <1μM range.92 Of note, the IC50 (0.565μM) and IC90 (2.63μM) values for brilacidin observed in the Calu-3 cell line are well below clinically-achievable concentrations based on pharmacokinetics observed in a Phase 2b clinical trial of brilacidin for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): median Cmax in plasma was 7.67μM brilacidin (free-base) from a single IV dose of 0.6 mg/kg.""
This would prove to be a HUGE benefit of BRIL and further distinguish its multi MOAs! The inclusion of Zika virus (ZIKV), WNV, DENV, HCV, and HIV-1 all being Intra Cellularly upregulated Virus would expand the potentail applications of BRIL...and ist VALUE!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151136/
RP
""While brilacidin’s mechanism of action appears primarily to be extracellular, it may also impact intracellular viral replication and is planned to be researched further. Supportive of this, an in silico quantum mechanical molecular screening study of 11,522 compounds identified brilacidin as a potential inhibitor of SARS-CoV-2 based on the potential of its physico-chemical properties to interfere with the intracellular replication of SARS-CoV-2’s main protease (Mpro).90
The high CC50 (a measure of cytotoxicity) and low IC50 (a measure of potency) values observed for brilacidin in Calu-3 cells—yielding a Selectivity Index (SI) for brilacidin of 426 (CC50=241μM/IC50=0.5 65μM)—strongly support brilacidin’s treatment potential to achieve positive antiviral outcomes in humans. A vast majority of other drugs being evaluated as potential COVID-19 treatments, including repurposed drugs, have SIs that are much lower than that achieved by brilacidin,91 with most drugs failing to show anti-SARS-CoV-2 potency in the <1μM range.92 Of note, the IC50 (0.565μM) and IC90 (2.63μM) values for brilacidin observed in the Calu-3 cell line are well below clinically-achievable concentrations based on pharmacokinetics observed in a Phase 2b clinical trial of brilacidin for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): median Cmax in plasma was 7.67μM brilacidin (free-base) from a single IV dose of 0.6 mg/kg.""
This would prove to be a HUGE benefit of BRIL and further distinguish its multi MOAs! The inclusion of Zika virus (ZIKV), WNV, DENV, HCV, and HIV-1 all being Intra Cellularly upregulated Virus would expand the potentail applications of BRIL...and ist VALUE!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151136/
RP
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