Continuing the studies of INCDSB to better understand the potential of drug repurposing in COVID-19, it was analyzed control strategies over essential host factors for SARS-CoV-2 infection. It was constructed comprehensive directed protein-protein interaction networks integrating the top ranked host factors, drug target proteins, and directed protein-protein interaction data. It was analyzed the networks to identify drug targets and combinations thereof that offer efficient control over the host factors. It was validated our findings against clinical studies data and bioinformatics studies. Our method offers a new insight into the molecular details of the disease and into potentially new therapy targets for it. Our approach for drug repurposing is significant beyond COVID-19 and may be applied also to other diseases.