Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continues to cause human infection and mortality worldwide. Currently, there are no specific viral protein-targeted therapeutics available. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear.

In this article, the authors have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, the authors data provides several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, which could guide the design of novel antiviral agents specifically targeting to SARS-CoV-2.

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Article reference: Sisi Kang, Mei Yang, Zhongsi Hong, Liping Zhang, Zhaoxia Huang, Xiaoxue Chen, Suhua He, Ziliang Zhou, Zhechong Zhou, Qiuyue Chen, Yan Yan, Changsheng Zhang, Hong Shan, Shoudeng Chen, Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites, Acta Pharmaceutica Sinica B, 2020, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2020.04.009

Keywords: COVID-19, Coronavirus, SARS-CoV-2, Nucleocapsid protein, RNA binding domain, Crystal structure, Antiviral targeting site

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

Acta Pharmaceutica Sinica B (APSB) is a monthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences — including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

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CiteScore: 10.5

Impact Factor: 7.097

5-Year Impact Factor: 7.865

Source Normalized Impact per Paper (SNIP): 2.210

SCImago Journal Rank (SJR): 1.792

ISSN 2211-3835