冠状病毒SARS-CoV和SARS-CoV-2基因组中的核糖核衣壳组装/包装信号：检测、比较和对治疗靶向的意义
Ribonucleocapsid assembly/packaging signals in the genomes of the coronaviruses SARS-CoV and SARS-CoV-2: Detection, comparison and implications for therapeutic targeting
摘要：
冠状病毒的基因组ssRNA被包装在螺旋状的核衣壳内。由于螺旋的过渡对称性，ssRNA和核衣壳蛋白之间的弱特异性合作相互作用导致相关基因组序列中特异性准周期组装/包装信号的自然选择。在冠状病毒SARS-CoV和SARS-CoV-2的基因组中检测到并重建了与核衣壳螺旋结构协调的这种信号。两种病毒信号的主要周期约为54 nt，这意味着每个N蛋白6.75 nt。核衣壳完全覆盖长度约30，000 nt的ssRNA基因组将需要4，400个N蛋白，这使得它们在结构蛋白中最丰富。SARS-CoV和SARS-CoV-2的基序库是不同的，但SARS-CoV-2的不同分离株几乎一致。我们获得了组装/包装信号在具有宽度为432 nt的非重叠窗口的基因组上的分布。最后，使用谱熵，我们比较了SARS-CoV和SARS-CoV-2在病毒年龄期间的点突变和插入缺失的负荷。我们发现SARS-CoV上的突变负荷更高。从这个意义上说，SARS-CoV-2可以被视为“新生”病毒。这些观察结果可能有助于实际的医学应用，并具有基本的意义。
英文摘要：
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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