The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity

• Published in: Biomolecules (Basel, Switzerland) Vol. 13; no. 7; p. 1095
• Main Authors: Labach, Daniel S, Kohio, Hinissan P, Tse, Edwin A, Paparisto, Ermela, Friesen, Nicole J, Pankovich, Jim, Bazett, Mark, Barr, Stephen D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Acquired immune deficiency syndrome; adenovirus; AIDS; Antimicrobial activity; Antiviral activity; Antiviral agents; BOLD-100; Cancer; Carbon dioxide; Cell culture; Clinical trials; COVID-19; Drug dosages; FDA approval; Health aspects; HIV; HIV-1; Hospitalization; Human immunodeficiency virus; Infections; Kinases; Ligands; Metabolism; Mortality; Organometallic compounds; Penicillin; Pharmacology, Experimental; Proteins; Reagents; Replication; RNA polymerase; ruthenium-based drug; SARS-CoV-2; Sequence analysis; Severe acute respiratory syndrome coronavirus 2; Transcription factors; Viruses; Canada; United States > US; COVID-19; HIV-1; SARS-CoV-2; BOLD-100; adenovirus; antiviral; ruthenium-based drug
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13071095

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 -[tetrachlorobis(1 -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.