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Innovation Pharmaceuticals (IPIX) reports today receiving data from a leading Public Health Research Institute (PHRI) showing Brilacidin inhibits SARS-CoV-2, the novel coronavirus responsible for COVID-19, in a human cell line. Brilacidin, in comparison to vehicle control, exhibited an inhibitory effect on SARS-CoV-2 in a dose-dependent manner—an average 29 percent inhibition at 0.1ug/ml (the lowest concentration) to an 85 percent inhibition at 100ug/ml (the highest concentration).
The Brilacidin anti-SARS-CoV-2 research being conducted at the PHRI is separate from research being performed at a U.S. Regional Biocontainment Laboratory (RBL), both with BSL-3 testing capabilities.
“This human cell line data is highly significant, with exciting implications,” commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. “We now have preliminary in vitro data from two separate independent laboratories that, cumulatively, support Brilacidin’s ability to act directly on the novel coronavirus, as a virucidal agent, and prevent viral binding to host cells. Across the coming weeks, we anticipate sharing additional anti-SARS-CoV-2 data from both research institutions as we work towards initiating a clinical study of Brilacidin for the treatment of COVID-19.”
For the experiment, the SARS-CoV-2 spike pseudotyped luciferase virus was incubated with Brilacidin at different concentrations—from a low of 0.1ug/ml to a high of 100ug/ml—for 1 hour before being added to HEK/293T cells (a human kidney cell line) expressing hACE2 for 2 hours. Then, the infected cells were cultured in media for 3 days before cells were lysed, with the inhibitory effect measured as a function of luciferase activity. Multiple measurements were taken to determine an average efficacy.
The primary investigator characterized the results as promising, especially given inhibitory effects in this particular human cell line are difficult to achieve based on the PHRI’s experience testing other defensins. The researcher also theorizes Brilacidin’s inhibitory effect may be partially due to the drug’s ability to prevent viral entry by blocking the SARS-CoV-2 Spike 1 (S1) Receptor-Binding Domain (RBD) from interacting with the Angiotensin-Converting Enzyme-2 (ACE2) receptor, the method by which the novel coronavirus gains entry into human cells. Additional anti-SARS-CoV-2 testing in human cell lines is underway at both the PHRI and the RBL to further elucidate Brilacidin’s antiviral properties.
Related, the article below highlights how defensins/peptides and their synthetic mimics, like Brilacidin, might be able to block the uptake of the novel coronavirus into host cells via the ACE2 receptor given their unique molecular properties. The article further points out that SARS-CoV-2 might be losing the battle in the intestines, in contrast to the lungs, due to defensins (present naturally) exerting a protective effect.
- “Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps.” CS Med. Chem. Lett. 2020. Published online May 18, 2020.https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00233 (pdf)
For researchers and institutions interested in collaborating on Brilacidin for COVID-19, please send inquiries to: [email protected]
Brilacidin and COVID-19
Brilacidin is one of the few drugs targeting COVID-19 that has been tested in Phase 2 human trials for other clinical indications, providing an established safety and efficacy profile, thereby potentially enabling it to rapidly help address the worldwide coronavirus crisis. Laboratory testing conducted at a U.S.-based Regional Biocontainment Laboratory (RBL), and at a Public Health Research Institute (PHRI), supports Brilacidin’s antiviral activity in directly inhibiting SARS-CoV-2 in cellular assays, with a molecular screening study of 11,552 compounds also supporting the drug as a promising novel coronavirus treatment. Additional pre-clinical and clinical data support Brilacidin’s potential to inhibit the production of IL-6, IL-1β, TNF-α and other pro-inflammatory cytokines and chemokines (MCP-1), which have been identified as central drivers in the worsening prognoses of COVID-19 patients. Brilacidin’s antimicrobial properties might also help to fight secondary bacterial infections, which can co-present in up to 20 percent of COVID-19 patients. These data collectively support Brilacidin as a particularly promising and unique (3 in 1 combination: antiviral, immune/anti-inflammatory, and antimicrobial) anti-COVID-19 therapeutic candidate.
