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 non‐canonical nucleic acids structures with distinct biofunctions. Here, we studied four putative G4‐forming sequences (PQSs) in SARS‐CoV‐2 genome. One of them (namely RG‐1), which locates in the coding sequence (CDS) region of SARS‐CoV‐2 nucleocapsid phosphoprotein (N), has been verified to form stable RNA G4 structure in live cells. G4‐specific compounds, such as PDP, can stabilize RG‐1 G4 and significantly reduce the protein levels of SARS‐CoV‐2 N by inhibiting its translation bothin vitro andin vivo. To our knowledge, this is the first evidence that PQSs in SARS‐CoV‐2 can form G4 structures in live cells, and their biofunctions can be regulated by G4‐specific stabilizer. We expect this finding will provide new insights into developing novel antiviral drugs against COVID‐19.
Πληροφορίες
Πέμπτη 17 Σεπτεμβρίου 2020
Targeting RNA G‐quadruplex in SARS‐CoV‐2: A Promising Therapeutic Target for COVID‐19?
Targeting RNA G‐quadruplex in SARS‐CoV‐2: A Promising Therapeutic Target for COVID‐19?:
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 non‐canonical nucleic acids structures with distinct biofunctions. Here, we studied four putative G4‐forming sequences (PQSs) in SARS‐CoV‐2 genome. One of them (namely RG‐1), which locates in the coding sequence (CDS) region of SARS‐CoV‐2 nucleocapsid phosphoprotein (N), has been verified to form stable RNA G4 structure in live cells. G4‐specific compounds, such as PDP, can stabilize RG‐1 G4 and significantly reduce the protein levels of SARS‐CoV‐2 N by inhibiting its translation bothin vitro andin vivo. To our knowledge, this is the first evidence that PQSs in SARS‐CoV‐2 can form G4 structures in live cells, and their biofunctions can be regulated by G4‐specific stabilizer. We expect this finding will provide new insights into developing novel antiviral drugs against COVID‐19.
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 non‐canonical nucleic acids structures with distinct biofunctions. Here, we studied four putative G4‐forming sequences (PQSs) in SARS‐CoV‐2 genome. One of them (namely RG‐1), which locates in the coding sequence (CDS) region of SARS‐CoV‐2 nucleocapsid phosphoprotein (N), has been verified to form stable RNA G4 structure in live cells. G4‐specific compounds, such as PDP, can stabilize RG‐1 G4 and significantly reduce the protein levels of SARS‐CoV‐2 N by inhibiting its translation bothin vitro andin vivo. To our knowledge, this is the first evidence that PQSs in SARS‐CoV‐2 can form G4 structures in live cells, and their biofunctions can be regulated by G4‐specific stabilizer. We expect this finding will provide new insights into developing novel antiviral drugs against COVID‐19.
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