A quantitative systems pharmacology (QSP) model of the pathogenesis and treatment of SARS-CoV-2 infection can inform and accelerate the development of novel medicines to treat COVID-19. Simulations of clinical trials allow in silico exploration of the uncertainties of clinical trial design and can rapidly inform protocol decisions. To this end, I will discuss the development of a QSP model of COVID-19 that was used to inform and accelerate the clinical development of nirmatrelvir, a novel SARS-CoV-2 protease inhibitor.