Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs

Area of Science:

• Cardiovascular Research
• Neuroscience
• Drug Discovery
• Virology

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 has led to significant global health challenges.
• Existing COVID-19 treatments may cause adverse drug reactions, necessitating safer alternatives.
• Repurposing FDA-approved drugs is a strategy to accelerate COVID-19 treatment development.

Purpose of the Study:

• To evaluate the cardiotoxicity and neurotoxicity of early-line anti-COVID-19 drugs.
• To investigate SARS-CoV-2 infection in cardiomyocytes and neurons using iPSC-derived cells.
• To establish a population-based drug screening platform for assessing drug safety.

Main Methods:

• Utilized 13 human leukocyte antigen (HLA) homozygous human induced pluripotent stem cell (iPSC) lines for drug screening.
• Infected iPSC-derived cardiomyocytes and neurons to study viral tropism and infection rates.
• Assessed cardiotoxicity and neurotoxicity of anti-COVID-19 drugs, including remdesivir, arbidol, hydroxychloroquine, and chloroquine.

Main Results:

• iPSC-derived cardiomyocytes express the ACE2 receptor, correlating with higher SARS-CoV-2 infection (r = 0.86).
• Neurons showed minimal ACE2 expression and low SARS-CoV-2 infection rates.
• Identified remdesivir and arbidol as cardiotoxic; arbidol, remdesivir, hydroxychloroquine, and chloroquine as neurotoxic.

Conclusions:

• The iPSC-based platform effectively assesses cell-specific SARS-CoV-2 infection and drug toxicity.
• The study identified specific cardiotoxic and neurotoxic anti-COVID-19 drugs.
• This platform aids clinicians in selecting safer treatment options for COVID-19 patients.