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

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 effect...

Full description

Saved in:
Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2023-07, Vol.13 (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: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
adenovirus
AIDS
Antimicrobial activity
Antineoplastic Agents - pharmacology
Antiviral activity
Antiviral agents
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
BOLD-100
Cancer
Carbon dioxide
Cell culture
Clinical trials
COVID-19
Drug dosages
FDA approval
Health aspects
HIV
HIV-1
Hospitalization
Human immunodeficiency virus
Humans
Infections
Kinases
Ligands
Metabolism
Mortality
Organometallic compounds
Pandemics
Penicillin
Pharmacology, Experimental
Proteins
Reagents
Replication
RNA polymerase
ruthenium-based drug
SARS-CoV-2
Sequence analysis
Severe acute respiratory syndrome coronavirus 2
Transcription factors
Virus Replication
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom13071095