ML2006a4, an orally active SARS-CoV-2 main protease (Mpro) inhibitor, exhibits potent activity with an IC50 in the picomolar range. This compound is cell permeable and demonstrates antiviral efficacy by inhibiting the replication of SARS-CoV-2 in Huh7.5.1-ACE2-TMPRSS2 (Huh7.5.1++) cells at picomolar concentrations [1].

ML2006a4 (0-10 μM) exhibits antiviral activity in Huh7.5.1++ and A549-ACE2 (A549+) cells, with EC50 values of 100 nM and 120 nM, respectively [1].

The pharmacokinetic profile of ML2006a4 (20 mg/kg, administered intravenously) indicates a plasma clearance (C pl) of 39 mL/min/kg and a steady-state volume of distribution (V ss) of 0.66 L/kg, with an oral bioavailability of 27% (40 mg/kg, orally) [1]. In SARS-CoV-2 MA10 infected BALB/c mice, ML2006a4 (40 mg/kg, orally, twice daily for 4 days) effectively reduces viral load and provides lung protection without significant toxicity [1]. The treatment results in decreased inflammation and respiratory epithelial injury, promotes epithelial regeneration, and enhances survival rates with minimal weight loss.