Figure 3.

Effects of clinically employed antiarrhythmic drugs on SARS-CoV-2 ORF 3a protein-mediated currents—class III antiarrhythmic drugs amiodarone and dofetilide block SARS-CoV-2 ORF 3a protein-mediated currents. (A) Representative macroscopic currents recorded under control conditions and after application of the respective antiarrhythmic drug as indicated (100 µM, 30 min) (B) Effects of the respective antiarrhythmics on SARS-CoV-2 ORF 3a protein-mediated currents, quantified at the end of the +80 mV test pulse (n = 3–6 cells). The drugs are arranged according to Vaughan Williams classes I–IV. Data are expressed as mean ± standard error of the mean from. (C and D) Time course of SARS-CoV-2 ORF 3a current inhibition by amiodarone (C) or dofetilide (D) and the partial reversibility of inhibition upon washout. In the right part of the panel, mean current levels are depicted: under control conditions, subsequent to a 30-min superfusion with the respective drug, and after a 20-min washout period. (E and F) Left: activation curves (total current amplitudes, quantified at the end of the 400 ms test pulse), investigated under isochronal recording conditions for control conditions and after administration of the respective drug. Center: normalized activation curves, investigated under isochronal recording conditions (current amplitudes normalized to the maximum current), investigated under isochronal recording conditions. Right: fraction of blocked step currents, plotted as function of the test pulse potential. Data are presented as mean ± standard error of the mean from n = 5 cells. Dotted lines represent zero current level, and scale bars are depicted as insets. Statistical significance is indicated by *, representing a P < 0.05 from two-tailed paired Student’s t-tests followed by Bonferroni correction.