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Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein

Science Bulletin. 2022-10; 
Xiaodong Luan, Xinming Li, Yufan Li, Gengchen Su, Wanchao Yin, Yi Jiang, Ning Xu, Feng Wang, Wang Cheng, Ye Jin, Leike Zhang, H. Eric Xu, Yi Xue, Shuyang Zhang
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Gene Synthesis The genes coding SARS-CoV-2 N-NTD (residues 48–173) and N-CTD (residues 250–365) were chemically synthesized with codon optimization (GenScript, Nanjing, China). Get A Quote

Abstract

Nucleocapsid (N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the formation of ribonucleoprotein (RNP) complex with the viral RNA. Here we reported the crystal structures of the N-terminal domain (NTD) and C-terminal domain (CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to the formation of the RNP complex. We also screened small molecule inhibitors of N-NTD and N-CTD and discovered that ceftriaxone sodium, an antibiotic, can block the binding of RNA to NTD and inhibit the formation ... More

Keywords

SARS-CoV-2, nucleocapsid protein, N-terminal domain, ceftriaxone sodium