Teriflunomide

Eight-week-old female C57BL/6 mice (19–21 g) were obtained from Janvier Labs (Saint Berthevin, France). The animals received either 50 mg/kg Molnupiravir (MedChemExpress LLC) twice daily, 10 mg/kg/day Teriflunomide (Biozol) or a mixture of 50 mg/kg twice daily Molnupiravir +10 mg/kg/day Teriflunomide via oral gavage in a volume of 2.5 mL/kg PEG400 (n = 3 per group). Molnupiravir was given twice daily with 8 h between first and second treatment each day. Formulations were freshly prepared before every application. At day one, PK samples were taken 0.5, 1, 2, 4, 6 and 8 h after the first dose. Compound concentrations were analyzed as in the hamster PK experiment.

Eight-week-old Syrian Gold hamsters (72–96 g) were obtained from Janvier Labs (Saint Berthevin, France). The animals received either 150 mg/kg Molnupiravir (MedChemExpress LLC) twice daily or 20 mg/kg/day Teriflunomide (Biozol) via oral application using a feeding pipet (n = 3 per group). Teriflunomide was formulated in 20% PEG400 (Roth), 2% Tween-80 (Sigma Aldrich), 39% peanut oil (Braendle) and 39% strawberry syrup (Yo); Molnupiravir was formulated in 10% PEG400, 2% Tween-80, 44% water and 44% strawberry syrup. Molnupiravir was given twice daily with 8 h between first and second treatment each day in an application volume of 4 mL/kg. Formulations were freshly prepared before every application. At day one, PK samples were taken 0.5, 1, 2, 4, 8 and 24 h after the first dose. Compound concentrations were analyzed in whole blood using liquid chromatography-mass spectrometry. For Molnupiravir, its active metabolite, EIDD-1931/NHC, was measured.