Abstract: Methods of modeling the in vivo efficacy of drug combinations for the treatment or prevention of viral infection are described. The described methods combine data for single drugs and drug combinations from pharmacokinetic, pharmacodynamic, and viral dynamics models under a series of estimated in vivo drug potencies to provide predictions of the in vivo effects of the drug combinations. These predictions can be used to more accurately select drugs and drug treatment regimens that can be successful in controlling viral infection in animal studies, clinical trials and in medical or veterinary interventions. Also described is a method of treating or preventing filovirus infections using combinations of orally available drugs based on predictions from the modeling methods.