Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design
文献类型：期刊论文
| 作者 | Xu, X; Liu, YQ; Weiss, S; Arnold, E; Sarafianos, SG; Ding, JP |
| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 2003 |
| 卷号 | 31期号:24页码:7117-7130 |
| 通讯作者 | Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, 320 Yue Yang Rd, Shanghai 200031, Peoples R China., |
| 英文摘要 | The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV plays a pivotal role in viral replication and is a potential target for anti-SARS therapy. There is a lack of structural or biochemical data on any coronavirus polymerase. To provide insights into the structure and function of SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps, and built a three-dimensional model of the catalytic domain. The structural model permits us to discuss the potential functional roles of the conserved motifs and residues in replication and their potential interactions with inhibitors of related enzymes. We predict important structural attributes of potential anti-SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the 2' and 3' groups of the sugar ring and C3' endo sugar puckering, and the absence of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1 reverse transcriptase. We propose that the clinically observed resistance of SARS to ribavirin is probably due to perturbation of the conserved motif A that controls rNTP binding and fidelity of polymerization. Our results suggest that designing anti-SARS therapies can benefit from successful experiences in design of other antiviral drugs. This work should also provide guidance for future biochemical experiments. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | DEPENDENT RNA-POLYMERASE ; HEPATITIS-C VIRUS ; ACUTE RESPIRATORY SYNDROME ; HIV-1 REVERSE-TRANSCRIPTASE ; PROTEIN SECONDARY STRUCTURE ; DOUBLE-STRANDED DNA ; CRYSTAL-STRUCTURE ; ANGSTROM RESOLUTION ; ACTIVE-SITE ; HONG-KONG |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000187659000007 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2387]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Xu, X,Liu, YQ,Weiss, S,et al. Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design[J]. NUCLEIC ACIDS RESEARCH,2003,31(24):7117-7130. |
| APA | Xu, X,Liu, YQ,Weiss, S,Arnold, E,Sarafianos, SG,&Ding, JP.(2003).Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design.NUCLEIC ACIDS RESEARCH,31(24),7117-7130. |
| MLA | Xu, X,et al."Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design".NUCLEIC ACIDS RESEARCH 31.24(2003):7117-7130. |
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