Network-based Drug Repurposing for Human Coronavirus

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

Drug combinations, offering increased therapeutic efficacy and reduced toxicity, play an important role in treating various viral infections [61] . However, our ability to identify and validate effective combinations is limited by a combinatorial explosion, driven by both the large number of drug pairs and dosage combinations. In our recent study, we proposed a novel network-based methodology to identify clinically efficacious drug combinations [25] . Relying on approved drug combinations for hypertension and cancer, we found that a drug combination was therapeutically effective only if it was captured by the 'Complementary Exposure' pattern: the targets of the drugs both hit the disease module, but target separate neighborhoods ( Figure 6A ). Here we sought to identify drug combinations that may provide a synergistic effect in treating HCoVs with welldefined mechanism-of-action by network analysis. For the 16 potential repurposable drugs ( Figure 5A) , we showcased three network-predicted candidate drug combinations in the potential treatment of HCoVs.