A recent academic paper posted (pdf) to the preprint server, medRxiv, shows SARS-CoV-2, the novel coronavirus responsible for COVID-19—which has led to over 1 million deaths worldwide as of this writing—suppresses defensins.
Based on the RT-PCR analysis of samples collected from the buccal cavity during screening for the SARS-CoV-2 infection, a number of defensin genes were shown to be downregulated, suggesting that the “innate immunity provided by defensins is or may be compromised.” The study authors go on to suggest “defensin peptides could be attractive therapeutic options.”
As announced today, the Company has been granted by the FDA a pre-IND meeting request for the study of Brilacidin, a defensin-mimetic drug candidate, for the treatment of COVID-19.
The proposed clinical trial comprises a Phase 2, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of Brilacidin in hospitalized patients with COVID-19. Target enrollment is 120 patients, with a planned interim analysis.
About Brilacidin and COVID-19
Brilacidin is one of the few drugs targeting COVID-19 that has been tested in human trials (a total of 8) for other clinical indications, providing an established safety and efficacy database on over 460 subjects, thereby potentially enabling it to rapidly help address the novel coronavirus crisis. Ongoing laboratory testing conducted at a U.S. Regional Biocontainment Laboratory (RBL), and at a Public Health Research Institute (PHRI), supports Brilacidin’s antiviral ability to safely inhibit SARS-CoV-2 in both human and animal cell lines. A molecular screening study of 11,552 compounds also supports Brilacidin as a promising novel coronavirus treatment. Additional pre-clinical and clinical data support Brilacidin’s potential to inhibit IL-6, IL-1β, TNF-α and other pro-inflammatory cytokines and chemokines, which have been identified as central drivers in the worsening prognoses of hospitalized COVID-19 patients. Brilacidin’s robust 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 unique 3 in 1 combination—antiviral, immuno/anti-inflammatory, and antimicrobial—anti-COVID-19 therapeutic candidate.
“Downregulation of several defensin genes suggests that innate immunity provided by defensins is or may be compromised in SARS-CoV-2 infection resulting in progression of the disease caused by the virus. Upregulation of defensin gene expression and use of defensin peptides could be attractive therapeutic interventions.”
Source: “Downregulation of Defensin genes in SARS-CoV-2 infection.” (pdf) Mohammed M Idris, Sarena Banu, Archana B Siva, Ramakrishnan Nagaraj. medRxiv 2020.09.21.20195537.