| ABSTRACT |
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Nucleoside/tide analogs have played a key role in the treatment of viral infections caused by DNA viruses such as herpes virus and hepatitis B virus. They also play a key role in treating RNA viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza virus, and most recently the coronavirus SARS-CoV-2, the pathogen causing the COVID-19 pandemic. Studies over the past several decades have significantly expanded our knowledge of the potential off-target effects of this class of compounds. These effects include inhibition of host nucleic acid polymerases such as human mitochondrial DNA polymerase γ (POL γ) and mitochondrial RNA polymerase (POLRMT) as well as perturbation of nucleotide metabolism, mitochondrial respiration, and dNTP/NTP pools. Importantly, suitable methods to evaluate the potential for these types of toxicities are currently available. In this webinar, Dr. Joy Feng provides a historical review of the discovery of safe and efficacious antiviral nucleoside/tide analogs and the lessons learned from failed clinical studies due to safety concerns. Dr. Feng also discusses the utility of a panel of biochemical and cell-based assays to assess toxicity-liability in the early drug discovery stage.
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