Building the virus–host interactome
We collected HCoV–host protein interactions from various literatures based on our sizeable efforts. The HCoV-associated host proteins of several HCoVs, including SARS-CoV, MERS-CoV, IBV, MHV, HCoV-229E, and HCoV-NL63 were pooled. These proteins were either the direct targets of HCoV proteins or were involved in critical pathways of HCoV infection identified by multiple experimental sources, including high-throughput yeast-two-hybrid (Y2H) systems, viral protein pull-down assay, in vitro co-immunoprecipitation and RNA knock down experiment. In total, the virus–host interaction network included 6 HCoVs with 119 host proteins (Supplementary Table S3).