The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity

作者：Fan, Shaorong; Sun, Wenju; Fan, Ligang; Wu, Nan; Sun, Wei; Ma, Haiqian; Chen, Siyuan; Li, Zitong; Li, Yu; Zhang, Jilin; Yan, Jian^*

来源：Computational and Structural Biotechnology Journal, 2022, 20: 5040-5044.

DOI：10.1016/j.csbj.2022.09.007

• SARS-CoV-2
• Nucleocapsid protein
• RNA binding specificity
• Coronavirus
• Conserved
• Virion assembly

The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 50- and 30-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the highthroughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other B-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both sequences are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

• 单位
  西北大学