Qin Lei, Xiong Bin, Luo Cheng, Guo Zong-Ming, Hao Pei, Su Jiong, Nan Peng, Feng Ying, Shi Yi-Xiang, Yu Xiao-Jing, Luo Xiao-Min, Chen Kai-Xian, Shen Xu, Shen Jian-Hua, Zou Jian-Ping, Zhao Guo-Ping, Shi Tie-Liu, He Wei-Zhong, Zhong Yang, Jiang Hua-Liang, Li Yi-Xue
Shanghai Center for Bioinformation Technology, Shanghai 201203, China.
Acta Pharmacol Sin. 2003 Jun;24(6):489-96.
To predict the probable genomic packaging signal of SARS-CoV by bioinformatics analysis. The derived packaging signal may be used to design antisense RNA and RNA interfere (RNAi) drugs treating SARS.
Based on the studies about the genomic packaging signals of MHV and BCoV, especially the information about primary and secondary structures, the putative genomic packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi-alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV and HCoV 229E. Secondary structures of RNA sequences were also predicted for the identification of the possible genomic packaging signals. Meanwhile, the N and M proteins of all five viruses were analyzed to study the evolutionary relationship with genomic packaging signals.
The putative genomic packaging signal of SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the most variable region of this gene. The RNA secondary structure of SARS-CoV genomic packaging signal is very similar to that of MHV and BCoV. The same result was also obtained in studying the genomic packaging signals of PEDV and HCoV 229E. Further more, the genomic sequence multi-alignment indicated that the locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other. It seems that the mutation rate of packaging signal sequences is much higher than the N protein, while only subtle variations for the M protein.
The probable genomic packaging signal of SARS-CoV is analogous to that of MHV and BCoV, with the corresponding secondary RNA structure locating at the similar region of ORF1b. The positions where genomic packaging signals exist have suffered rounds of mutations, which may influence the primary structures of the N and M proteins consequently.
通过生物信息学分析预测严重急性呼吸综合征冠状病毒(SARS-CoV)可能的基因组包装信号。所推导的包装信号可用于设计治疗SARS的反义RNA和RNA干扰(RNAi)药物。
基于对鼠肝炎病毒(MHV)和牛冠状病毒(BCoV)基因组包装信号的研究,特别是关于一级和二级结构的信息,利用生物信息学工具分析SARS-CoV的推定基因组包装信号。对SARS-CoV、MHV、BCoV、猪流行性腹泻病毒(PEDV)和人冠状病毒229E(HCoV 229E)的基因组序列进行多序列比对。还预测了RNA序列的二级结构以鉴定可能的基因组包装信号。同时,分析了所有五种病毒的N蛋白和M蛋白,以研究它们与基因组包装信号的进化关系。
SARS-CoV的推定基因组包装信号位于开放阅读框1b(ORF1b)的3'端,靠近MHV和BCoV的包装信号位置,该区域是该基因最易变的区域。SARS-CoV基因组包装信号的RNA二级结构与MHV和BCoV非常相似。在研究PEDV和HCoV 229E的基因组包装信号时也得到了相同的结果。此外,基因组序列多序列比对表明,SARS-CoV、PEDV和HCoV包装信号的位置相互重叠。包装信号序列的突变率似乎远高于N蛋白,而M蛋白只有细微变化。
SARS-CoV可能的基因组包装信号与MHV和BCoV类似,相应的RNA二级结构位于ORF1b的相似区域。基因组包装信号存在的位置经历了多轮突变,这可能会影响N蛋白和M蛋白的一级结构。