Atlas of interactions between SARS-CoV-2 macromolecules and host proteins
Guangnan Li,
Zhidong Tang,
Weiliang Fan,
Xi Wang,
Li Huang,
Yu Jia,
Manli Wang,
Zhihong Hu,
Yu Zhou
Affiliations
Guangnan Li
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China
Zhidong Tang
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China
Weiliang Fan
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China
Xi Wang
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
Li Huang
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China
Yu Jia
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China
Manli Wang
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
Zhihong Hu
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
Yu Zhou
College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China; State Key Laboratory of Virology, Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China; Institute for Advanced Studies, Wuhan University, Wuhan, China; Corresponding author. College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China.
The proteins and RNAs of viruses extensively interact with host proteins after infection. We collected and reanalyzed all available datasets of protein-protein and RNA-protein interactions related to SARS-CoV-2. We investigated the reproducibility of those interactions and made strict filters to identify highly confident interactions. We systematically analyzed the interaction network and identified preferred subcellular localizations of viral proteins, some of which such as ORF8 in ER and ORF7A/B in ER membrane were validated using dual fluorescence imaging. Moreover, we showed that viral proteins frequently interact with host machinery related to protein processing in ER and vesicle-associated processes. Integrating the protein- and RNA-interactomes, we found that SARS-CoV-2 RNA and its N protein closely interacted with stress granules including 40 core factors, of which we specifically validated G3BP1, IGF2BP1, and MOV10 using RIP and Co-IP assays. Combining CRISPR screening results, we further identified 86 antiviral and 62 proviral factors and associated drugs. Using network diffusion, we found additional 44 interacting proteins including two proviral factors previously validated. Furthermore, we showed that this atlas could be applied to identify the complications associated with COVID-19. All data are available in the AIMaP database (https://mvip.whu.edu.cn/aimap/) for users to easily explore the interaction map.