Targeting RNA G-Quadruplex in SARS-CoV-2: A Promising Therapeutic Target for COVID-19?
Chuanqi Zhao
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorGeng Qin
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorJingsheng Niu
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorZhao Wang
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorChunyu Wang
State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012 P. R. China
Search for more papers by this authorProf. Jinsong Ren
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Xiaogang Qu
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorChuanqi Zhao
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorGeng Qin
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
These authors contributed equally to this work.
Search for more papers by this authorJingsheng Niu
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorZhao Wang
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorChunyu Wang
State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012 P. R. China
Search for more papers by this authorProf. Jinsong Ren
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Xiaogang Qu
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022 P. R. China
University of Science and Technology of China, Hefei, Anhui, 230026 P. R. China
Search for more papers by this authorAbstract
The COVID-19 pandemic caused by SARS-CoV-2 has become a global threat. Understanding the underlying mechanisms and developing innovative treatments are extremely urgent. G-quadruplexes (G4s) are important noncanonical nucleic acid structures with distinct biofunctions. Four putative G4-forming sequences (PQSs) in the SARS-CoV-2 genome were studied. One of them (RG-1), which locates in the coding sequence region of SARS-CoV-2 nucleocapsid phosphoprotein (N), has been verified to form a stable RNA G4 structure in live cells. G4-specific compounds, such as PDP (pyridostatin derivative), can stabilize RG-1 G4 and significantly reduce the protein levels of SARS-CoV-2 N by inhibiting its translation both in vitro and in vivo. This result is the first evidence that PQSs in SARS-CoV-2 can form G4 structures in live cells, and that their biofunctions can be regulated by a G4-specific stabilizer. This finding will provide new insights into developing novel antiviral drugs against COVID-19.
Conflict of interest
The authors declare no conflict of interest.
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