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Introduction
In the twenty-first century, the COVID-19 pandemic was triggered by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a single-stranded RNA virus with a rapid transmission rate and a high infection rate. This has led to widespread global infections and elevated mortality rates1. SARS-CoV-2 represents the third coronavirus in recent decades to infect humans, following the outbreaks of SARS and Middle East Respiratory Syndrome (MERS). During the outbreak, numerous treatment approaches were employed, including several drug classes, and convalescent plasma therapy, often in combination with invasive and non-invasive oxygen support1. Due to the lack of specific antivirals for COVID-19, researchers have turned to drug repurposing, utilizing previously approved antiviral agents to combat the rapid spread of the virus2.
Remdesivir (REM), chemically identified as 2-Ethylbutyl (2S)-2-[[(S)-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl] methoxy](phenoxy)phosphoryl]amino]propanoate (Fig. 1)3, is a prodrug that is metabolized into its active form, GS-441524, upon administration. GS-441524 inhibits viral RNA-dependent RNA polymerase by competing with ATP for RNA incorporation, thereby blocking RNA transcription and reducing viral RNA replication4. This mechanism grants REM broad-spectrum antiviral activity against several RNA viruses, including the Ebola virus, MERS-CoV, SARS-CoV, and SARS-CoV-25. The emergence of SARS-CoV-2 in 2019 renewed interest in REM due to its antiviral properties. It was the first drug to demonstrate efficacy against SARS-CoV-2 in clinical trials, leading to its approval for COVID-19 treatment by the FDA and the European Medicines Agency6. REM’s mechanism of action and broad antiviral spectrum make it a pivotal component of antiviral therapy, with ongoing research exploring its potential use in combination therapies7.
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Fig. 1
Suggested degradation pathway of Remdesivir.
Due to its near-complete first-pass metabolism, REM exhibits poor oral bioavailability and is thus administered intravenously (IV). It is typically infused in 0.9% saline over 30 to 120 min. The maximum plasma concentrations (Cmax) of REM and its primary metabolite, GS-441524, have been reported in the ranges of 2610–5440 ng/mL and 140–150 ng/mL, respectively8. REM is an inhibitor of several cytochrome P450 enzymes, potentially leading to numerous drug interactions when included in treatment regimens8. For example, REM may reduce the metabolism of aminophylline and the excretion of acyclovir4....