Posted elsewhere by "thekidzcollegephund": Acce

Posted elsewhere by "thekidzcollegephund":

Accepted Abstract submission for the MHSRS conference in September 2022.

look at the last line of the abstract from Dr Aarthi Narayaan

Quote:

---

Quote:Brilacidin has also undergone several clinical studies for multiple indications, using different routes of administration, and has a known safety profile in humans.

---

Quote:Abstract ID: MHSRS-22-05925
Submitter Details:
Affiliation:INDUSTRY
Status:Civilian, Other (Non-Government)
Namer. Aarthi Narayanan
Primary Email:aarthin@gmail.com
Secondary Email:aarthin@gmail.com
Phone703) 365-2700 ext. 2315
Organization:American Type Culture Collection
Manassas, VA 20110
United States
Presenter Details:
Affiliation:INDUSTRY
Status:Civilian, Other (Non-Government)
Namer. Aarthi Narayanan
Primary Email:aarthin@gmail.com
Secondary Email:aarthin@gmail.com
Phone703) 365-2700 ext. 2315
Organization:American Type Culture Collection
Manassas, VA 20110
United States
Co-Authors Detail:
Carol Anderson1, Michael Barrera2, Niloufar Boghdeh2, Kyle Weston3, Jane Harness3, Aarthi Narayanan1

1American Type Culture Collection

2George Mason University

3Innovation Pharmaceuticals





Abstract Details:
Breakout Sessionevelopment of New Front Line Therapies to Prevent & Treat Endemic Viral Diseases (non SARS CoV-2)
Submission Category:Oral Presentation
Title:Brilacidin, a host defense peptide mimetic, is a broad-spectrum countermeasure strategy against acutely infectious viruses
Abstract:
Introduction: Acutely infectious viruses including those that are transmissible by the respiratory and aerosol routes pose critical threats to the warfighter and the civilian population. Aerosol-transmissible pathogens, such as bunyaviruses (Rift Valley fever virus [RVFV]), and alphaviruses (Venezuelan Equine Encephalitis Virus [VEEV], Eastern Equine Encephalitis Virus [EEEV]), have broad range of host tropism, retain high rates of infectivity as aerosols, attain high viral load in the host over short periods of time, cause damage to the blood brain barrier (BBB), impact neurological integrity and are likely to contribute to organ damage due to extreme inflammation. These viruses pose nontrivial challenges to the warfighter because no FDA-approved therapeutics or vaccines are currently available that can be rapidly scaled up, field-deployed and thus potentially mitigate the deleterious consequences of inflammation in addition to decreasing viral load. The long-term neurological sequelae that can ensue from these acute viral infections, especially by the aerosol route, can lead to a life-long health burden for the warfighter. These pathogens are also naturally transmitted by mosquito vectors and are known to cause zoonotic disease in animals in addition to affecting humans on an annual basis in the United States and in other parts of the world. This situation could further drive mutations, leading to infectious spillover events between species. There is an urgent, unmet need for broad-spectrum intervention strategies that can ideally control the disease manifestations in the host and the spread of disease as a prophylactic countermeasure. Our ongoing studies with brilacidin, a host defense peptide (HDP)-based mimetic, have successfully demonstrated that brilacidin is able to interfere with viral integrity and exert an antiviral effect in vitro against candidate alphaviruses and bunyavirus. Furthermore, early indications support the potential of brilacidin to also act in an anti-inflammatory capacity by its impact on inflammatory cytokine expression.
Methods: Appropriate cell lines (Vero cells, U87MG cells, HSAE cells, Huh7, and HepG2 cells) were infected with RVFV (MP-12 strain), VEEV (TC-83 and TrD strains) and SINV +/- brilacidin. Culture supernatants and nucleic acid lysates were quantified for extracellular and intracellular viral load and impact on infectivity by plaque and qRT-PCR assays. Impact of brilacidin on cell viability and lack of toxicity were ascertained by CellTiter Glo assay. Impact of treatment on inflammatory events were quantified by a combination of PCR (gene expression) and ELISA (protein expression). Early studies involving cell biological mechanisms have involved transmission electron microscopy of virus distribution in infected cells +/- brilacidin.
Results: Our studies to query any potential cytotoxicity and quantify CC50 values for brilacidin have indicated that the compound is very well tolerated by a wide breadth of cell lines including those of neuronal origin. The CC50 values for brilacidin in some representative cell types are: Veros: 64.90 µM U87MGs >100 µM, HSAECs: 61.32 µM, Huh7s: 12.03 µM, HepG2s: 153.3 µM. Studies that queried the antiviral activities of brilacidin were also tailored to address mechanism of action and target validation. For candidate alphaviruses and bunyavirus, the following treatment conditions were assessed: pre-treatment only (Pre), pre-treatment + post-treatment (Pre+Post), virus-incubation only (Virus), pre-treatment + virus-incubation + post treatment (Pre + V + Post). For VEEV, our data demonstrated that in both Vero cells and U87MG astrocytes, the Pre + V + Post treatment strategy resulted in >1 log reduction of infectious virus in the culture supernatant. For SINV, an old-world alphavirus, we noticed a higher inhibitory impact on the viral load (> 2 logs) than what was observed in the case of new world alphaviruses. For RVFV, the Pre + V + Post treatment produced the highest antiviral outcome with a decrease in viral load of >2.5 logs. Ongoing studies are focused on obtaining the inhibition profile for EEEV in astrocytes and microglial cells. Our overall assessment of brilacidin targets suggest that brilacidin exerts an impact on the virion integrity directly for several viruses, although the sensitivity to brilacidin differs for different viruses (SARS-CoV-2>RVFV>VEEV). Brilacidin appears to exert its greatest antiviral effect when the virus is directly exposed to brilacidin. Quantification of anti-inflammatory activities in VEEV infection by ELISA demonstrated decrease in IL-1b and IL-6 levels when treated with brilacidin. Early assessments of virus distribution in TC-83-infected cells by electron microscopy is suggestive of potentially lower intracellular viral load upon treatment. Assessment of innate immune activities included quantification of interferon gamma expression by PCR in the context of RVFV infection, which did not indicate a statistically significant change in IFN-ß at the gene expression level. Additional ongoing studies are focused on assessment of brilacidin treatment on a broader array of inflammation-associated genes. Impact of brilacidin on maintenance of BBB integrity in the context of endothelial cells will also be investigated.

Conclusions: The observations that we continue to make in experiments involving brilacidin in the context of acutely infectious viruses support the idea of brilacidin functioning in a broad-spectrum capacity as an antiviral compound. Several lines of evidence suggest that brilacidin may affect virion integrity and hence impact viral entry, thus positioning it well as a broad-spectrum prophylactic countermeasure solution. The observations about anti-inflammatory activities indicate that intracellular events are also modulated by brilacidin treatment that exert a combined protective effect by decreasing viral and inflammatory load. Brilacidin has also undergone several clinical studies for multiple indications, using different routes of administration, and has a known safety profile in humans.

Disclaimer:
Learning Objectives
1. To understand the broad-spectrum potential of brilacidin against aerosol-transmissible acute viruses.
2. To evaluate the mechanism(s) of antiviral activities of brilacidin against enveloped viruses.
3. To ascertain the anti-inflammatory potential of brilacidin in the context of acute virus infections.