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

https://doi.org/10.1016/j.apsb.2020.04.009Get rights and content
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Abstract

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. 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. Herein, we 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, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Graphical abstract

The crystal structure of the N-terminal RNA-binding domain of SARS-CoV-2 nucleocapsid protein was determined by X-ray. Compared with other previously reported coronavirus nucleocapsid protein N-terminal domains, the authors have identified a unique potential RNA-binding pocket that can guide the design of novel antiviral drugs targeting SARS-CoV-2.

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Key words

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

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Peer review under the responsibility of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.