COVID‐19 metabolism: Mechanisms and therapeutic targets
Tianshi Wang,
Ying Cao,
Haiyan Zhang,
Zihao Wang,
Cheuk Him Man,
Yunfan Yang,
Lingchao Chen,
Shuangnian Xu,
Xiaojing Yan,
Quan Zheng,
Yi‐Ping Wang
Affiliations
Tianshi Wang
Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Department of Biochemistry and Molecular Cell Biology Shanghai Jiao Tong University School of Medicine Shanghai China
Ying Cao
State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Haiyan Zhang
Bai Jia Obstetrics and Gynecology Hospital Shanghai China
Zihao Wang
Fudan University Shanghai Cancer Center Key Laboratory of Breast Cancer in Shanghai Shanghai Key Laboratory of Radiation Oncology Cancer Institute and The Shanghai Key Laboratory of Medical Epigenetics Institutes of Biomedical Sciences Shanghai Medical College Fudan University Shanghai China
Cheuk Him Man
Division of Hematology Department of Medicine University of Hong Kong Pokfulam Hong Kong, China
Yunfan Yang
Department of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan China
Lingchao Chen
Department of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration Neurosurgical Institute of Fudan University Shanghai Clinical Medical Center of Neurosurgery Shanghai China
Shuangnian Xu
Department of Hematology Southwest Hospital Army Medical University Chongqing China
Xiaojing Yan
Department of Hematology The First Affiliated Hospital of China Medical University Shenyang China
Quan Zheng
Center for Single‐Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine Shanghai China
Yi‐Ping Wang
Fudan University Shanghai Cancer Center Key Laboratory of Breast Cancer in Shanghai Shanghai Key Laboratory of Radiation Oncology Cancer Institute and The Shanghai Key Laboratory of Medical Epigenetics Institutes of Biomedical Sciences Shanghai Medical College Fudan University Shanghai China
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.
