The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity
Daniel S. Labach,
Hinissan P. Kohio,
Edwin A. Tse,
Ermela Paparisto,
Nicole J. Friesen,
Jim Pankovich,
Mark Bazett,
Stephen D. Barr
Affiliations
Daniel S. Labach
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Hinissan P. Kohio
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Edwin A. Tse
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Ermela Paparisto
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Nicole J. Friesen
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
Jim Pankovich
Bold Therapeutics Inc., 422 Richards St, Suite 170, Vancouver, BC V6N 2Z4, Canada
Mark Bazett
Bold Therapeutics Inc., 422 Richards St, Suite 170, Vancouver, BC V6N 2Z4, Canada
Stephen D. Barr
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 5C1, Canada
The COVID-19 pandemic has highlighted an urgent need to discover and test new drugs to treat patients. Metal-based drugs are known to interact with DNA and/or a variety of proteins such as enzymes and transcription factors, some of which have been shown to exhibit anticancer and antimicrobial effects. BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]dihydrate) is a novel ruthenium-based drug currently being evaluated in a Phase 1b/2a clinical trial for the treatment of advanced gastrointestinal cancer. Given that metal-based drugs are known to exhibit antimicrobial activities, we asked if BOLD-100 exhibits antiviral activity towards SARS-CoV-2. We demonstrated that BOLD-100 potently inhibits SARS-CoV-2 replication and cytopathic effects in vitro. An RNA sequencing analysis showed that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.
