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Monday, 02/07/2022 2:07:49 AM

Monday, February 07, 2022 2:07:49 AM

Post# of 5468
Appears that Brilicidin is still being researched for Covid-19 remediation possibilities. This report was recently updated Here:

https://www.biorxiv.org/content/10.1101/2021.11.04.467344v1.full.pdf+html


Yanmei Hu, Hyunil Jo, William F. DeGrado, View ORCID ProfileJun Wang
doi: https://doi.org/10.1101/2021.11.04.467344
Now published in Journal of Medical Virology doi: 10.1002/jmv.27616

INTRODUCTION Seven coronaviruses are known to infect human beings. Human coronavirus (HCoV)-229E, -NL63, -OC43 and -HKU1 account for 15~30% cases of common cold worldwide 1,
while severe acute respiratory syndrome coronavirus (SARS-CoV) 2, Middle East Respiratory Syndrome (MERS-CoV) 3, and severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2)-the causative agent of COVID-19 4, are three highly pathogenic human coronaviruses that cause acute severe respiratory syndrome.
As the third coronavirus that causes severe respiratory disease, SARS-CoV-2 associated COVID19 has led to more than 211 million infections and over 4.4
million deaths worldwide, and more than 37 million infections and over 627 thousand deaths in the U.S. alone as of Aug 21, 2021 5. Currently, two mRNA vaccines
are authorized for COVID-19: BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.), and a third single-dose COVID-19 vaccine JNJ-78436735 (Johnson & Johnson) was
issued for Emergency Use Authorization. Although vaccine continues to be a mainstay for viral prophylaxis, the efficacy of vaccine might be compromised with emerging
variants such as the delta variant 6-8. For this reason, small molecular antiviral drugs are important complements of vaccines to help combat pandemics. Host defense
peptides (HDPs), also called antimicrobial peptides (AMPs), are typically small peptides (12-50 amino acids) that are expressed in neutrophils and mucosa and serve as
the first line of defense against foreign pathogens 9. HDPs have been extensively explored as antibiotics 10, antivirals 11, antifungals 12 and anticancer agents 13.
Most HDPs share an amphiphilic structure with a positively charged face and a hydrophobic face 14. It is proposed that HDPs disrupt bacterial cell
membranes by .CC-BY 4.0 International licenseavailable under a(which was not certified by peer review) is the author/funder, who has granted bioRxiv
a license to display the preprint in perpetuity. It is made The copyright holder for this preprintthis version
posted November 5, 2021. ; https://doi.org/10.1101/2021.11.04.467344doi: bioRxiv preprint
interacting with the negatively charged phospholipid headgroups 15-17. Brilacidin is a small synthetic HDP mimetic 18, and
has potent antibacterial activity against both Gram-positive and Gram-negative bacteria, and is currently in Phase 2 clinical
trials (Clinical Trials NCT01211470, NCT020388, and NCT02324335). The antibacterial mechanisms of action of brilacidin include both
membrane disruption and immunomodulation 19, 20. Brilacidin is also in clinical trial (NCT04784897) as a SARS-CoV-2 antiviral drug
candidate for hospitalized COVID-19 patients. A recent study showed that brilacidin exhibited potent inhibitory effect on SARS-CoV-2
replication (EC50=0.565 µM/CC50=241 µM), and the proposed mechanism of action is through disrupting viral integrity, thereby blocking viral
entry 21. However, the effect of brilacidin on host cell and the antiviral activity of brilacidin against other HCoVs have not been
investigated. In this work, we showed that brilacidin inhibits SARS-CoV-2 pseudovirus entry into multiple cell lines. However, acetyl brilacidin
had no inhibition on SARS-CoV-2 pseudovirus entry, and heparin, a heparan sulfate proteoglycans (HSPGs) mimetic, diminished the inhibitory
activity of brilacidin. This result suggests that brilacidin has an additional mechanism of action by binding to HSPGs on the host cell,
thereby blocking viral attachment. HSPGs have been reported as an attachment factor for SARS-CoV-2

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