The PBPK LeiCNS-PK3.0 framework predicts Nirmatrelvir (but not Remdesivir or Molnupiravir) to achieve effective concentrations against SARS-CoV-2 in human brain cells

·No information exists on the pharmacokinetics of antiCOVID-19 drugs in human brain.·LeiCNS-PK3.0 framework predicts adequately the human brain pharmacokinetic profiles.·Nirmatrelvir is predicted to reach effective brain concentrations against COVID-19.·Ineffective brain concentrations are predicted for Molnupiravir and Remdesivir.·LeiCNS-PK3.0 is a promising tool to optimize and accelerate CNS drug development.