Little in vitro effect of remdesivir on mitochondrial respiration and monoamine oxidase activity in isolated mitochondria.

Remdesivir (RDV) is a novel antiviral drug whose mitochondrial effects are not well known. In vitro effects of RDV on the mitochondrial respiration, individual respiratory complexes, and the activity of monoamine oxidase (MAO-A and MAO-B) were measured in isolated mitochondria. At micromolar RDV concentrations, minimal or no inhibitory effects on the studied mitochondrial enzymes were found. At very high concentrations of RDV, there was partial inhibition of complex I- (IC50 675 μmol/L, residual activity 39.4 %) and complex II-linked (IC50 81.8 μmol/L, residual activity 40.7 %) respiration, without inhibition of complex IV-linked respiration, and partial inhibition both of MAO-A (IC50 26.6 μmol/L, residual activity 35.2 %) and MAO-B (IC50 89.8 μmol/L, residual activity 34.0 %) activity. Individual respiratory complexes (I, II + III, and IV) were partially inhibited at a high drug concentration. The active metabolite of RDV (GS-443902) had very little effect on mitochondrial oxygen consumption rate with residual activity of 87.0 % for complex I-linked respiration, 90.3 % for complex II-linked respiration, and with no inhibition of complex IV-linked respiration. In conclusion, measurement of the effect of RDV and its active metabolite on isolated mitochondria shows that there is very little direct effect on mitochondrial respiration occurs at therapeutic drug concentration.