My response
What is most interesting you and others have focused on 1 chart and ignored the whole body of the research. In addition you and others have attributed efficacy to Remdesivir which it does not possess.
The Discussion on page 10 outlines the results of the study:
1. "All experiments conducted in Vero and Calu-3 cell line models were supportive of an early inhibition exerted by brilacidin on SARS-CoV-2, indicating the drug’s impact on viral integrity. The idea that brilacidin directly interferes with the integrity of the virion is further supported by the observation that when drug treatment was limited to the virus alone (Figure 2E), with no treatment of host cells, a robust decrease of viral load was still observed in both the Washington strain and the Italian strainof SARS-CoV-2."
This is consistent with claims Brilacidin is virucidal. It quickly attacks the virus before it enters the cell.
2. "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 = 0.565µM)—strongly support brilacidin’s treatment potential to possibly achieve positive antiviral outcomes in humans clinical trials."
This statement reflects the low toxicity and high potency of Brilacidin against Covid 19. The high SI number supports positive outcomes in human clinical trials
3. In the combination studies Brilacidin and Remdesivir 2.5 um demonstrated synergy in vitro
https://www.mdpi.com/1999-4915/13/2/271
The reality is the 2.5 um dose is easily achievable in vivo by Brilacidin which obtained a median C-max in the ABSSSI study of 7.67 um and is well above its IC 50 of .565um.
https://www.biorxiv.org/content/10.1101/2020....450v1.full
Remdesivir's IC 50 in vitro is .77um, but it has to enter the host cells to prevent intracellular viral reproduction. Remdesivir is a prodrug and is converted inside the cell to its active metabolite, Nuc-TP, which is estimated to have an IC 50 of 38um to 231um or 7.7um in other studies, well above that of Brilacidin's IC 50 of .565um.
Its pharmacology explains Remdesivir's poor clinical performance in spite of a relatively good in vitro IC 50.
In addition Remdesivir's hepatotoxicity limits higher dosing.
"Assuming similar distribution and accumulation ratios of remdesivir and Nuc-TP in the lung between humans and monkeys, an optimistic estimation of Nuc-TP in the human lung tissues is 2 to 3-fold higher at a steady state than that observed in the monkey lung tissues [1]. This suggests that an IV dose of 200 mg remdesivir in a human may only achieve a suboptimal concentration of active form of Nuc-TP of <?2–5 µM in the human lung tissues (TableIII). Given that the intracellular volume (0.54 l) is 46% of the total volume of the lung (1.17 l) [17], the intracellular concentration of Nuc-TP in the human lung may be only at 4–10 µM (TableIII), which may be below the estimated intracellular IC50 and IC90 of Nuc-TP. Unfortunately, systemic adverse effects such as hepatotoxicity preclude escalation of the remdesivir dose to more than 200 mg/day."
The following article demonstrates these findings in great detail.
https://link.springer.com/article/10.1208/s12248-020-00459-8
GLTA Farrell
What is most interesting you and others have focused on 1 chart and ignored the whole body of the research. In addition you and others have attributed efficacy to Remdesivir which it does not possess.
The Discussion on page 10 outlines the results of the study:
1. "All experiments conducted in Vero and Calu-3 cell line models were supportive of an early inhibition exerted by brilacidin on SARS-CoV-2, indicating the drug’s impact on viral integrity. The idea that brilacidin directly interferes with the integrity of the virion is further supported by the observation that when drug treatment was limited to the virus alone (Figure 2E), with no treatment of host cells, a robust decrease of viral load was still observed in both the Washington strain and the Italian strainof SARS-CoV-2."
This is consistent with claims Brilacidin is virucidal. It quickly attacks the virus before it enters the cell.
2. "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 = 0.565µM)—strongly support brilacidin’s treatment potential to possibly achieve positive antiviral outcomes in humans clinical trials."
This statement reflects the low toxicity and high potency of Brilacidin against Covid 19. The high SI number supports positive outcomes in human clinical trials
3. In the combination studies Brilacidin and Remdesivir 2.5 um demonstrated synergy in vitro
https://www.mdpi.com/1999-4915/13/2/271
The reality is the 2.5 um dose is easily achievable in vivo by Brilacidin which obtained a median C-max in the ABSSSI study of 7.67 um and is well above its IC 50 of .565um.
https://www.biorxiv.org/content/10.1101/2020....450v1.full
Remdesivir's IC 50 in vitro is .77um, but it has to enter the host cells to prevent intracellular viral reproduction. Remdesivir is a prodrug and is converted inside the cell to its active metabolite, Nuc-TP, which is estimated to have an IC 50 of 38um to 231um or 7.7um in other studies, well above that of Brilacidin's IC 50 of .565um.
Its pharmacology explains Remdesivir's poor clinical performance in spite of a relatively good in vitro IC 50.
In addition Remdesivir's hepatotoxicity limits higher dosing.
"Assuming similar distribution and accumulation ratios of remdesivir and Nuc-TP in the lung between humans and monkeys, an optimistic estimation of Nuc-TP in the human lung tissues is 2 to 3-fold higher at a steady state than that observed in the monkey lung tissues [1]. This suggests that an IV dose of 200 mg remdesivir in a human may only achieve a suboptimal concentration of active form of Nuc-TP of <?2–5 µM in the human lung tissues (TableIII). Given that the intracellular volume (0.54 l) is 46% of the total volume of the lung (1.17 l) [17], the intracellular concentration of Nuc-TP in the human lung may be only at 4–10 µM (TableIII), which may be below the estimated intracellular IC50 and IC90 of Nuc-TP. Unfortunately, systemic adverse effects such as hepatotoxicity preclude escalation of the remdesivir dose to more than 200 mg/day."
The following article demonstrates these findings in great detail.
https://link.springer.com/article/10.1208/s12248-020-00459-8
GLTA Farrell
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