Efforts to develop antiviral drugs versus COVID-19 or vaccines for its prevention have been hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. This talk will describe our efforts to address this challenge by expressing 26 of the 29 SARS-CoV-2 proteins in human cells and identifying the human proteins physically associated with each using affinity-purification mass spectrometry. Among 332 high-confidence SARS-CoV-2-human protein-protein interactions, we identified 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Within a subset of these, multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity.