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Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
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Abstract
Abstract The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. 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 is yet to be clear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with 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.
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Metadata
- Authors
- Kang, S., Yang, M., Hong, Z., Zhang, L., Huang, Z., Chen, X., He, S., Zhou, Z., Zhou, Z., Chen, Q., Yan, Y., Zhang, C., Shan, H., & Chen, S.
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 10
- Issue
- 7
- Pages
- 1228-1238
- ISSN
- 2211-3835 (ISSN-L)
- OpenAlex
- W3016553966
- Cited by
- 632
- References
- 43
- FWCI
- 16.36
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
- Funders
- National Natural Science Foundation of China (31770801)
- Chinese Academy of Sciences
- National Key Research and Development Program of China (81870019, SQ2018YFC090075)
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- Kang, S., Yang, M., Hong, Z., Zhang, L., Huang, Z., Chen, X., He, S., Zhou, Z., Zhou, Z., Chen, Q., Yan, Y., Zhang, C., Shan, H., & Chen, S. (2020). Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2020.04.009
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