Key result
Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density, whereas acute exposure had no effect.
Why the study?
Remdesivir has been linked to QTc prolongation and torsade de pointes in case reports, but data are conflicting regarding its inhibition of hERG-related current.
Does remdesivir or its metabolite GS-441524 inhibit hERG-related potassium currents in vitro?
Does remdesivir or its metabolite GS-441524 inhibit hERG-related potassium currents in vitro?
Prolonged exposure to remdesivir inhibits hERG potassium currents in vitro, providing a potential mechanistic explanation for clinical reports of QTc prolongation.
Prolonged remdesivir may inhibit hERG and contribute to QTc risk; leaves open clinical relevance and need for in vivo confirmation.
Remdesivir, approved for the treatment of COVID-19, has been associated with heart-rate corrected QT interval (QTc) prolongation and torsade de pointes in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related gene (hERG) -related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney 293 cells stably expressing hERG were treated with various concentrations of remdesivir and GS-441524. The effects of acute and prolonged exposure on hERG-related current were assessed using whole-cell configuration of voltage-clamp protocols. Acute exposure to remdesivir and GS-441524 had no effect on hERG currents and the half-activation voltage (V 1/2 ). Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density. The propensity for remdesivir to prolong QTc intervals and induce torsade de pointes in predisposed patients warrants further investigation.
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Amarh et al. (2023) studied this question. Remdesivir and GS-441524 was evaluated on hERG-related current (peak tail currents and hERG current density). Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density, whereas acute exposure had no effect.
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