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Angew Chem Int Ed Engl ; 60(1): 432-438, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-774564

ABSTRACT

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.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , G-Quadruplexes/drug effects , RNA, Viral/drug effects , SARS-CoV-2/drug effects , Drug Evaluation, Preclinical , Gene Expression Regulation, Viral/drug effects , Genome, Viral , Humans , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/drug effects , Protein Folding , SARS-CoV-2/genetics , Small Molecule Libraries , Temperature
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