Toxicity of antiviral Remdesivir on human liver’s ATP binding cassette subfamily D member 3 transporters

Abstract

Background and objective: The World Health Organization advises against the use of the antiviral drug Remdesivir to treat severe COVID-19 infections due to potential toxicity. The molecular mechanism of this toxicity is not well established. ATP-binding cassette (ABC) transporters play an essential role in the transport of various drugs in many illnesses. Objective: This study examines the possible role of ATP-binding cassette, subfamily D, member 3 (ABCD3) in Remdesivir toxicity. Methods: Real-time PCR and MTT assays were used to demonstrate the toxicity of Remdesivir on ABCD3 gene expression in the HepG2 cell line. Enzyme-linked immunosorbent assay was used to detect serum ABCD3 levels, Prestige24i was used to detect C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum. Nano-Checker710 was used to detect D-dimer in the serum of the patients. Results: Remdesivir exhibits dose-dependent toxicity to the HepG2 cell line. The drug toxicity is significantly increased at three doses of 5, 10, and 20 µg/ml in virus-free hepatic cell lines. It suppressed ABCD3 gene expression in both the HepG2 cell line and COVID-19 patients’ sera. COVID-19 virus increases serum levels of CRP, ALT, AST and D-dimer. The drug lowers serum CRP, transiently lowers D-dimer, and increases ALT and AST levels. Conclusion: Remdesivir suppressed ABCD3 gene expression and increased levels of inflammatory markers. Remdesivir contributes to hepatocyte damage independently of the COVID-19 virus.