Phylogenomics and bioinformatics of SARS-CoV.
Phylogenomics and bioinformatics of SARS-CoV.
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DOI：
10.1016/j.tim.2004.01.005
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发表时间：
2004-03
影响因子：
15.9
通讯作者：
Goldman N
中科院分区：
文献类型：
--
作者：
Liò P;Goldman N
使用系统发育方法追踪冠状病毒分子变化的历史可以提供对序列修饰模式的有力见解，这些修饰模式是SARS-CoV（严重急性呼吸道综合征冠状病毒）基因组中选择压力和分子功能改变的基础。冠状病毒科，包括SARS冠状病毒，之间的系统发育关系的拓扑结构和分支长度，已估计使用复制酶多聚蛋白。已发现刺突蛋白片段S1（参与受体结合）和S2（参与膜融合）具有不同的突变率。片段S1可以进一步分为两个区域（S1 A，其包含大约前400个核苷酸，和S1 B，其包含接下来的280个核苷酸），这两个区域也显示出不同的突变率。基于S1 B的遗传学研究表明，SARS-CoV与MHV（鼠肝炎病毒）密切相关，已知MHV与鼠受体CEACAM 1结合。预测的结构，可访问性和突变率的S1 B区也提出。由于基于S2七肽的抗SARS药物半衰期短且难以制造，我们的研究结果表明S1 B区域可能对抗SARS药物的发现感兴趣。
Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The topology and branch lengths of the phylogenetic relationships among the family Coronaviridae, including SARS-CoV, have been estimated using the replicase polyprotein. The spike protein fragments S1 (involved in receptor-binding) and S2 (involved in membrane fusion) have been found to have different mutation rates. Fragment S1 can be further divided into two regions (S1A, which comprises approximately the first 400 nucleotides, and S1B, comprising the next 280) that also show different rates of mutation. The phylogeny presented on the basis of S1B shows that SARS-CoV is closely related to MHV (murine hepatitis virus), which is known to bind the murine receptor CEACAM1. The predicted structure, accessibility and mutation rate of the S1B region is also presented. Because anti-SARS drugs based on S2 heptads have short half-lives and are difficult to manufacture, our findings suggest that the S1B region might be of interest for anti-SARS drug discovery.
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