Network-based Drug Repurposing for Human Coronavirus

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

Viruses (including HCoV) require host cellular factors for successful replication during infections [1] . Systematic identification of virus-host protein-protein interactions (PPIs) offers an effective way toward elucidation of the mechanisms of viral infection [14, infections [1] , including SARS-CoV [16] , MERS-CoV [16] , Ebola virus [17] , and Zika virus [13, [18] [19] [20] . We recently presented an integrated antiviral drug discovery pipeline that incorporated gene-trap insertional mutagenesis, known functional drug-gene network, and bioinformatics analyses [13] . This methodology allows to identify several candidate repurposable drugs for Ebola virus [10, 13] . Our work over the last decade has demonstrated how network strategies can, for example, be used to identify effective repurposable drugs [12, [21] [22] [23] [24] and drug combinations [25] for multiple human diseases. For example, network-based drug-disease proximity that sheds light on the relationship between drugs (e.g., drug targets) and disease modules (molecular determinants in disease pathobiology modules within the PPIs), and can serve as a useful tool for efficient screening of potentially new indications for approved drugs, as well as drug combinations, as demonstrated in our recent studies [12, 22, 25] .