In Vitro and In Vivo Characterization of the Metallodrug BOLD-100 as an Inhibitor of SARS-CoV-2 Replication
Abstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused extensive mortality and societal disruption. BOLD-100 is a novel anticancer therapeutic being considered to treat COVID-19. We hypothesized that BOLD-100 inhibits SARS-CoV-2 replication and progression of COVID-19. Using Western blotting, quantitative RT-PCR, and cell viability assays, we determined that BOLD-100 inhibits SARS-CoV-2 replication in vitro. RNA sequencing analysis demonstrated that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. Intravenous BOLD-100 treatment of SARS-CoV-2-infected hamsters did not significantly alter body weight, lung viral load or pathological lesions. Finally, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2 and can also inhibit replication of Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a novel antiviral agent and will inform its future preclinical development.