论文标题

冠状病毒SARS-COV和SARS-COV-2的基因组中的核糖核酸组件/包装信号:检测,比较和对治疗靶向的影响

Ribonucleocapsid assembly/packaging signals in the genomes of the coronaviruses SARS-CoV and SARS-CoV-2: Detection, comparison and implications for therapeutic targeting

论文作者

Chechetkin, Vladimir R., Lobzin, Vasily V.

论文摘要

冠状病毒的基因组ssRNA被包装在螺旋核蛋白质中。由于螺旋的过渡对称性,SSRNA和核素蛋白之间的弱特异性合作相互作用会导致相关基因组序列中特定的准周期组装/包装信号的自然选择。在冠状病毒SARS-COV和SARS-COV-2的基因组中检测并重建了与Nucleocapsid螺旋结构协调的信号。两种病毒的主要信号的主要时期约为54 nt,这意味着每N蛋白6.75 nt。由核素的完全覆盖长度约为30,000 nt的ssRNA基因组需要4,400 N蛋白,这使得它们在结构蛋白中最丰富。 SARS-COV和SARS-COV-2的基序的曲目有分歧,但几乎是SARS-COV-2的不同分离株的几乎是重合的。我们获得了带有宽度432 NT的非重叠窗口的基因组上组装/包装信号的分布。最后,使用光谱熵,我们比较了SARS-COV和SARS-COV-2在病毒年龄期间点突变和indels的负载。我们发现SARS-COV上的突变负荷较高。从这个意义上讲,SARS-COV-2可以视为“新生儿”病毒。这些观察结果可能有助于实用医疗应用,并且具有基本兴趣。

The genomic ssRNA of coronaviruses is packaged within a helical nucleocapsid. Due to transitional symmetry of a helix, weakly specific cooperative interaction between ssRNA and nucleocapsid proteins leads to the natural selection of specific quasi-periodic assembly/packaging signals in the related genomic sequence. Such signals coordinated with the nucleocapsid helical structure were detected and reconstructed in the genomes of the coronaviruses SARS-CoV and SARS-CoV-2. The main period of the signals for both viruses was about 54 nt, that implies 6.75 nt per N protein. The complete coverage of ssRNA genome of length about 30,000 nt by the nucleocapsid would need 4,400 N proteins, that makes them the most abundant among the structural proteins. The repertoires of motifs for SARS-CoV and SARS-CoV-2 were divergent but nearly coincided for different isolates of SARS-CoV-2. We obtained the distributions of assembly/packaging signals over the genomes with non-overlapping windows of width 432 nt. Finally, using the spectral entropy, we compared the load from point mutations and indels during virus age for SARS-CoV and SARS-CoV-2. We found the higher mutational load on SARS-CoV. In this sense, SARS-CoV-2 can be treated as a "newborn" virus. These observations may be helpful in practical medical applications and are of basic interest.

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