Bold Therapeutics, a clinical-stage biopharmaceutical company, recently generated additional data supporting rapid clinical development of BOLD-100 as a novel antiviral. In a series of experiments conducted by Dr. Stephen Barr, Associate Professor in the Department of Microbiology and Immunology at Western University, both BOLD-100 and remdesivir were tested head-to-head in a cytopathic effect assay against a live Wuhan strain of SARS-CoV-2 (COVID-19) in Vero E6 cells. Consistent with prior experiments, BOLD-100 showed low nanomolar IC50 values, a magnitude lower (1/10th) than the IC50 values of Gilead’s remdesivir, the only currently approved therapeutic for COVID-19. This data clearly demonstrates that BOLD-100 is a highly potent antiviral agent.
BOLD-100 is a first-in-class ruthenium-based small molecule drug which selectively inhibits stress-induced upregulation of the chaperone protein GRP78. In cancer, GRP78 plays a critical role in resistance, survival and proliferation, whereas in viral infections, GRP78 plays a critical role in host recognition, viral entry and viral replication. There are now more than two hundred independent academic articles highlighting the critical role that GRP78 plays in viral infections (e.g. Ha DP, Van Krieken R, Carlos AJ, Lee AS. The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection. J Infect. 2020 Sep;81(3):452–82.).
This empirical data on BOLD-100 as an antiviral is supported by additional work carried out by Bold Therapeutics’ other COVID-19 Consortium members including Franois Jean, PhD, Associate Professor in the Department of Microbiology and Immunology and founder of the UBC Facility for Infectious Disease and Epidemic Research (FINDER); Ted Steiner, MD, Professor and Division Head, Division of Infectious Diseases at the University of British Columbia; Marc-Andr Langlois, Faculty Professor of Medicine at the University of Ottawa and Canada Research Chair in Molecular Virology and Intrinsic Immunity; and Len Seymour, PhD, Director of Clinical Pharmacology at the University of Oxford. Bold Therapeutics is also collaborating with international researchers at McMaster University, the University of Southern California, the University of Pennsylvania, Georgetown University, Queens University Belfast, the University of Vienna, and the Medical University of Vienna, among others who are collectively advancing our understanding of both the GRP78 pathway and BOLD-100’s selective inhibition of stress-induced GRP78.
“Bold Therapeutics’ ongoing collaboration with some of the top virologists in Canada continues to produce independent data supporting BOLD-100 as a novel antiviral