Abstract P3120: Cardio And Neurotoxicity Of Repurposed Anti-COVID-19 Drugs

Abstract

In December 2019, the novel coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread around the globe resulting in ~435 million confirmed cases and ~6 million related deaths as of March 2022, according to the World Health Organization. To combat COVID-19 quickly, there have been many attempts to repurpose current FDA-approved drugs or to revive old drugs with anti-viral properties. However, aside from the biological stress imposed by the virus, many of the current treatment options have been known to cause adverse drug reactions. We established a population-based human induced pluripotent stem cell drug screening platform to assess the toxicity of the first line of anti-COVID-19 drugs and to understand viral infection of cardiomyocytes and neurons. We found that iPSC-derived cardiomyocytes express the ACE2 receptor which correlated with a higher infection of the SARS-CoV-2 virus (r=0.86). However, ACE2 expression was undetectable in neurons which correlated with low infection of neurons. We then assessed the toxicity of anti-COVID-19 drugs and identified two cardiotoxic compounds (remdesivir and arbidol) and 4 neurotoxic compounds (arbidol, remdesivir, hydroxychloroquine, and chloroquine) which were validated by dose-response curves. These data show that this platform can quickly and easily be employed to further our understanding of cell-specific infection and identify drug toxicity of potential treatment options helping clinicians better decide on treatment options.