ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2
Qiaoxi Xia, Mantong Chen, Xiao Ge Zhou, Ling Lin, Yan Zhao, Xiaoqi Zheng, Meihui Huang, Shaohong Wang, Zepeng Du · Research Square · 2020
Abstract Background The novel coronavirus SARS-CoV-2 pandemic has infected more than 10 million people, killed over 500,000 so far. Currently, no effective drugs are available to treat this infectious disease, due to limited knowledge of the molecular mechanisms of SARS-CoV-2 infection. ACE2 (angiotensin I converting enzyme 2) has long been identified as the major receptor for coronavirus entry the host cells. Methods In this study, we constructed the protein-protein interaction networks (PPIN) based on ACE2 and its interacting proteins, combined with the expression change and co-expression relationship. The potential drugs targeting the proteins in the PPIN were explored.Results ACE2 and its interacting proteins AAMP and HRAS are obviously increased, and their PPIN show distinguishing expression patterns during the COVID-19 progression. At least six pathways are activated for the host cell in the response to the virus. Moreover, drug-target networks were built to provide important clues to block ACE2 and its interacting proteins. Except the reported four drugs for ACE2, its interacting protein CALM1 and HRAS are great potentially druggable. We also considered the path initiated from ACE2 to nucleus by cascades of interaction, especially for the transcription factors in the PPIN which are also druggable. Conclusion In summary, this study provides new insight into the disruption of the biological response to virus mediated by ACE2, but also its cascade interacting proteins when considering of PPIN.