In total, we computationally identified 135 drugs that were associated (Z < −1.5 and P < 0.05, permutation test) with the HCoV–host interactome (Fig. 4a, Supplementary Tables S4 and 5). To validate bias of the pooled cellular proteins from six CoVs, we further calculated the network proximities of all the drugs for four CoVs with a large number of know host proteins, including SARS-CoV, MERS-CoV, IBV, and MHV, separately. We found that the Z-scores showed consistency among the pooled 119 HCoV-associated proteins and other four individual CoVs (Fig. 4b). The Pearson correlation coefficients of the proximities of all the drugs for the pooled HCoV are 0.926 vs. SARS-CoV (P < 0.001, t distribution), 0.503 vs. MERS-CoV (P < 0.001), 0.694 vs. IBV (P < 0.001), and 0.829 vs. MHV (P < 0.001). These network proximity analyses offer putative repurposable candidates for potential prevention and treatment of HCoVs.
Fig. 4 A discovered drug-HCoV network.
a A subnetwork highlighting network-predicted drug-HCoV associations connecting 135 drugs and HCoVs. From the 2938 drugs evaluated, 135 ones achieved significant proximities between drug targets and the HCoV-associated proteins in the human interactome network. Drugs are colored by their first-level of the Anatomical Therapeutic Chemical (ATC) classification system code. b A heatmap highlighting network proximity values for SARS-CoV, MERS-CoV, IBV, and MHV, respectively. Color key denotes network proximity (Z-score) between drug targets and the HCoV-associated proteins in the human interactome network. P value was computed by permutation test.