The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity.
The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity.
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核衣壳蛋白高度保守的RNA结合特异性有助于鉴定具有广泛抗冠状病毒活性的药物
DOI：
10.1016/j.csbj.2022.09.007
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发表时间：
2022
影响因子：
6
通讯作者：
Yan, Jian
中科院分区：
文献类型：
--
作者：
Fan, Shaorong;Sun, Wenju;Fan, Ligang;Wu, Nan;Sun, Wei;Ma, Haiqian;Chen, Siyuan;Li, Zitong;Li, Yu;Zhang, Jilin;Yan, Jian
SARS-CoV-2核衣壳（N）蛋白与基因组RNA的5′端和3′端的结合具有不同的意义，这是由于其在病毒体组装过程中与中心区域的结合。然而，选择性结合的机制仍然未知。在此，我们进行了高通量RNA-SELEX（HTR-SELEX），以确定各种SARS-CoV-2变异体以及其他β-冠状病毒的N蛋白的RNA结合特异性，并显示N蛋白可以结合两个不相关的序列，这两个序列在所有变异体和物种中高度保守。有趣的是，这两个序列在人类转录组中几乎不存在;然而，它们在冠状病毒基因组中表现出高度富集、相互互补的分布，突出了它们在基因组包装中的不同功能。我们的研究结果提供了对病毒基因组包装的机制见解，从而增加了通过靶向N蛋白结合RNA开发具有广谱抗冠状病毒活性的药物的可行性。
The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5′- and 3′-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 high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other β-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.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
DOI：
10.1016/j.jbc.2022.101677
发表时间：
2022-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Cascarina SM;Ross ED
通讯作者：
Ross ED
影响因子：
7.7
作者：
Nitta KR;Jolma A;Yin Y;Morgunova E;Kivioja T;Akhtar J;Hens K;Toivonen J;Deplancke B;Furlong EE;Taipale J
通讯作者：
Taipale J
M蛋白与严重急性呼吸综合征相关的冠状病毒的其他结构蛋白之间的相互作用。
影响因子：
11
作者：
Hsieh YC;Li HC;Chen SC;Lo SY
通讯作者：
Lo SY