Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 1, Pages 432-438Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202011419
Keywords
drug discovery; inhibitors; G-quadruplex; RNA; viruses
Categories
Funding
- National Key R&D Program of China [2019YFA0709202]
- Natural Science Foundation of China [21533008, 91856205, 21820102009, 21871249, 21877105]
- Key Program of Frontier of Sciences (CAS) [QYZDJ-SSW-SLH052]
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Researchers found that specific sequences in the SARS-CoV-2 genome can form G4 structures, and their biofunctions can be regulated by specific compounds, providing new insights for developing novel antiviral drugs against COVID-19.
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.
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