Network-based Drug Repurposing for Human Coronavirus

Yadi Zhou; Yuan Hou; Jiayu Shen; Yin Huang; William Martin; Feixiong Cheng

HCoV, its target proteins should be within or in the immediate vicinity of the corresponding subnetwork in the human interactome (Figure 1) , as we demonstrated in multiple diseases [12, 21, 22, 25] using this drug repurposing strategy. We used a state-ofthe-art network proximity measure to quantify the relationship between HCoV-specific subnetwork ( Figure 3A ) and drug targets in the human protein-protein interactome. We constructed a drug-target network by assembling target information for more than 2,000 FDA-approved or experimental drugs (see Methods). To improve the quality and completeness of the human protein interactome network, we integrated PPIs with five types of experimental data: (1) binary PPIs from 3D protein structures; (2) binary PPIs from unbiased high-throughput yeast-two-hybrid assays; (3) experimentally identified kinase-substrate interactions; (4) signaling networks derived from experimental data; and (5) literature-derived PPIs with various experimental evidences (see Methods). We used a Z-score (Z) measure and permutation test to reduce the study bias in network proximity analyses (including hub nodes in the human interactome network by literaturederived PPI data bias) as described in our recent studies [12, 25] .