COVID-19 Drugs: Canada’s New Antiviral BOLD-100 Beats Remdesivir In Vitro Studies Involving SARS-CoV-2 Infected Vero E6 Cells

COVID-19 Drugs: Canadian based Bold Therapeutics, a clinical-stage biopharmaceutical company, have recently generated more key data supporting the rapid clinical development of a new therapeutic drug called BOLD-100 as an antiviral against the SARS-CoV-2 coronavirus.


 
The therapeutic drug BOLD-100 is a first-in-class ruthenium-based small molecule drug which selectively inhibits stress-induced upregulation of the chaperone protein GRP78.
 
In a new research 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.
 
As with previous studies, 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 new data clearly demonstrates that BOLD-100 is a highly potent antiviral agent.
 
It has been found that in cancer, GRP78 receptors play 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.
 
Currently there are now more than a 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 most recent study by researchers from University of Southern California was published in the Journal Of Infection highlighted the role of GRP78 as a potential therapeutic target for SARs-CoV-2 coronavirus infection. https://www.journalofinfection.com/article/S0163-4453(20)30398-4/fulltext#%20 or https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289740/
 
The critical empirical data on BOLD-100 as an antiviral is supported by additional work carried out by Bold Therapeutics' other COVID-19 Consortium members including Dr François Jean, PhD, Associate Professor in the Department of Microbiology and Immunology and founder of the UBC Facility for Infectious Disease and Epidemic Research (FINDER); Dr Ted Steiner, MD, Professor and Division Head, Division of Infectious Diseases at the University of British Columbia; Dr Marc-André Langlois, Faculty Professor of Medicine at the University of Ottawa and Canada Research Chair in Molecular Virology and Intrinsic Immunity; and Dr 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.
 
Dr Mark Bazett, Bold Ther apeutics' Director of Preclinical Development told Thailand Medical News, "Bold Therapeutics' ongoing collaboration with some of the top virologists in Canada continues to produce independent data supporting BOLD-100 as a novel antiviral. This new data is particularly impressive, showing that BOLD-100 is substantially more potent as an antiviral than remdesivir, the only recently Health Canada approved treatment for COVID-19. The collective evidence on BOLD-100 supports further, rapid development of this novel treatment option to support patients with COVID-19."

Although much attention has been given to vaccine development, it is a challenging and high-risk endeavor. And even if an effective vaccine is successfully developed and subsequently manufactured, effective antivirals for infected patients unable or unwilling to take vaccines will still be needed.
 
The new drug BOLD-100 has the potential to substantially reduce severity of infection, shortening hospital stays and reducing morbidity and mortality but this can only be definitively determined through clinical testing.
 
Most importantly, BOLD-100 could be effective against not just the current pandemic, but also future viral pandemics whereas COVID-19 vaccines would necessarily be ineffective.
 
Canada-based Bold Therapeutics has already manufactured more than sufficient drug product to support immediate clinical studies in COVID-19 due to an ongoing Phase 1/2 trial of BOLD-100 in combination with FOLFOX in the treatment of advanced GI cancers, with an open IND with the U.S. FDA and a February 2020 NOL from Health Canada.
 
Significantly in an earlier Phase 1 dose-escalation study of 46 patients with advanced cancer, BOLD-100 was safe and well-tolerated, potentially allowing BOLD-100 to move immediately into Phase 2 trials in COVID-19. These factors allow BOLD-100 to be developed and potentially approved as an anti-COVID-19 therapeutic in a relevant timeframe, rather than years from now.
 
Unfortunately whereas a lot of money is being thrown into vaccine developments based on hearsay and unproven data, small and medium sized drug companies or biotech startups developing antivirals against the SARS-CoV-2 coronavirus including Bold Therapeutics are still facing difficulties seeking proper fundings despite supporting studies and data, reflecting the fact that many pharma giants, governments and corporate capitalists especially Americans are still dictating the drug development market and suppressing lots of potential therapeutics over greed and monopolistic control. Expensive toxic drugs with very little proven efficacy are being heavily promoted over cheaper non-patented drugs that can be repurposed  or cheap supplements and herbs and cheaper drugs under development with more proven efficacy over the SARS-CoV-2 coronavirus and the various medical conditions it creates in the human host.
 
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