Abstract published in MHSRS website:
( this is the abstract details that was going to be given by the innovations Pharma team in the Military Health System Research Symposium. )
Abstract ID: MHSRS-21-04263
Submitter Details:
Affiliation:ACADEMIA
Status:Civilian, Other (Non-Government)
Name:Mr. Michael Barrera
Primary Email:mbarrer@gmu.edu
Secondary Email:
Phone:7867185908
Organization:George Mason University
Manassas, VA 20110
United States
Presenter Details:
Affiliation:ACADEMIA
Status:Civilian, Other (Non-Government)
Name:Mr. Michael Barrera
Primary Email:mbarrer@gmu.edu
Secondary Email:
Phone:7867185908
Organization:George Mason University
Manassas, VA 20110
United States
Abstract Co-Authors Detail:
Michael D. Barrera1,
Allison Bakovic1,
Miata Smith1,
Warren K. Weston, PhD2, (innovations pharma emp )
Jane A. Harness, PhD2, ( innovations pharma emp)
Aarthi Narayanan, PhD1
1National Center for Biodefense and Infectious Diseases, George Mason University , Manassas, VA
2Innovation Pharmaceuticals Inc. , Wakefield, MA
Abstract Details:
Breakout Session:Development of New Front Line Therapies to Prevent & Treat non SARS CoV-2 Endemic Viral Diseases
Submission Category:Oral Presentation
Title:Brilacidin, a host defense protein/peptide (HDP) mimetic, is a broad spectrum inhibitor of acutely infectious viruses
Abstract:
Acutely infectious viruses, such as encephalitic alphaviruses, are a threat to the warfighter due to their aerosolization capability and lack of FDA-approved countermeasures. The ongoing global COVID-19 pandemic has also drawn widespread attention to the health risks posed by respiratory pathogens, which have enormous potential to inflict morbidity and mortality on civilian and military populations alike. There is an urgent need to develop safe and effective broad spectrum antivirals, which can be administered prophylactically and therapeutically. In addition, the inflammatory damage associated with acute viral infections, as observed in encephalitic alphavirus and coronaviruses, necessitate the development of robust anti-inflammatory strategies that can prevent organ damage and ameliorate long-term disease sequelae. Brilacidin (PMX-30063) is a synthetic, non-peptidic small molecule mimetic of Host Defense Proteins/Peptides (HDPs) Building on “first principles” in medicinal chemistry and by leveraging sophisticated informatics to fine-tune physico-chemical properties and structure-activity relationships, Brilacidin overcomes the shortcomings and challenges that have complicated the clinical development of natural HDPs, including: proteolytic degradation, toxicity, lack of efficacy, malabsorption, and high cost to produce. Successful clinical trials have shown Brilacidin exhibiting potent antibacterial activity in Phase 2 clinical trials for treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI), and anti-inflammatory activity demonstrated in Phase 2 clinical trials for treatment of Ulcerative Proctitis/Ulcerative Proctosigmoiditis. Brilacidin received FDA Fast Track designation for the potential treatment of COVID-19 and currently is undergoing a Phase 2 clinical trial for treatment of moderate-to-severe COVID-19 in hospitalized patients. We have previously demonstrated decreased viral load using Brilacidin against SARS-COV-2 in ACE2 positive human cells in vitro, and the observed antiviral activity appears to disrupt viral integrity and block viral entry. Brilacidin achieved 90% inhibition of SARS-CoV-2 in Calu-3 cells at a concentration of 2.63µM and 50% inhibition at 0.565µM, yielding a high Selectivity Index of 426, further supporting in vivo and clinical studies. Moreover, we have demonstrated synergism of Brilacidin with Remdesivir, a current frontline COVID-19 antiviral against SARS-CoV-2, suggesting potential as a combinational therapeutic approach. More recently, we evaluated Brilacidin efficacy against other enveloped viruses such as the alphavirus, Venezuelan equine encephalitis virus (VEEV), a category B select pathogen. Early studies suggest robust inhibition of viral load against the VEEV TC-83 strain using Brilacidin in vitro. Ongoing studies are focused on expanding the inhibitory potential of Brilacidin in the context of fully virulent strains of VEEV and Eastern equine encephalitic virus (EEEV).
Disclaimer:W.K.W. serves as a consultant for Innovation Pharmaceuticals Inc. J.A.H. is an employee of Innovation Pharmaceuticals Inc.
Learning Objectives
Attendee will be able to describe Host Defense Proteins/Peptides (HDPs) and synthetic, non-peptidic small molecule mimetic of HDPs and how they relate to each other.
Attendee will able to recognize encephalitic alphaviruses and the threat they pose to warfighter due to their aerosolization capability.
Attendee will be able to analyze the effects of Brilacidin on viral replication and its potential use as a therapeutic.
