Ayub Ambreen, Ashfaq Usman A, Idrees Sobia, Haque Asma
Department of Bioinformatics and Biotechnology, Government College University , Faisalabad, Pakistan .
Biores Open Access. 2013 Oct;2(5):392-6. doi: 10.1089/biores.2013.0022.
The dengue virus (DENV) genome encodes 10 different genes including the NS3 gene, which has a protease and helicase domain used in virus replication. This domain is a potential target for antiviral agents against dengue. Due to a high mutation rate, DENV is classified into four major serotypes (DENV1-DENV4). This study was designed to perform conservancy analysis of all four serotypes by drawing a consensus sequence for each serotype and then drawing a global consensus sequence to study conserved residues in all four serotypes. A total of 127 NS3 sequences belonging to all four serotypes were retrieved and aligned using multiple alignment feature of CLC Workbench and were subjected to phylogenetic tree construction. Conservancy analysis of NS3 revealed conserved peptides with active site residues that can be important in developing antiviral agents against dengue virus. Among conserved residues, residues G142, Ser144, and G145 (catalytic pocket residues), A219, D220, and D221 (divalent cations binding residues), and His56, Asp79, Ser144, 146 were highly conserved among all the serotypes. Residues from L138 to L149 and from L226 to L245 were also considerably conserved in all serotypes, while lysine141 mutated to serine in serotype 3. A total of 14 peptides from the conserved regions of DENV NS3 protein were identified, which may be helpful to develop peptide inhibitors. The DENV NS3 phylogenetic tree showed the evolutionary relationship among all four serotypes, and all serotypes of dengue were found to have evolved from the dengue 4 serotype. Because of its high variability, DENV has become a global health concern. It is important to study residues that are present in protease, helicase, the catalytic pocket Mg(2+) binding site, and the AAA domain. This study revealed peptides with active site residues that are highly conserved among all four serotypes. These regions of the NS3 sequence may be helpful in developing antiviral agents.
登革病毒（DENV）基因组编码10种不同的基因，包括NS3基因，该基因具有用于病毒复制的蛋白酶和解旋酶结构域。这个结构域是抗登革热抗病毒药物的潜在靶点。由于高突变率，DENV被分为四种主要血清型（DENV1 - DENV4）。本研究旨在通过为每种血清型绘制一个共有序列，然后绘制一个全局共有序列来研究所有四种血清型中的保守残基，从而对所有四种血清型进行保守性分析。总共检索到属于所有四种血清型的127个NS3序列，并使用CLC Workbench的多重比对功能进行比对，然后构建系统发育树。NS3的保守性分析揭示了具有活性位点残基的保守肽段，这些残基在开发抗登革病毒的抗病毒药物中可能很重要。在保守残基中，G142、Ser144和G145残基（催化口袋残基）、A219、D220和D221残基（二价阳离子结合残基）以及His56、Asp79、Ser144、146在所有血清型中高度保守。L138至L149以及L226至L245的残基在所有血清型中也相当保守，而血清型3中的赖氨酸141突变为丝氨酸。总共鉴定出14个来自DENV NS3蛋白保守区域的肽段，这可能有助于开发肽抑制剂。DENV NS3系统发育树显示了所有四种血清型之间的进化关系，并且发现所有登革热血清型均从登革热4血清型进化而来。由于其高变异性，DENV已成为全球健康问题。研究蛋白酶、解旋酶、催化口袋Mg(2+)结合位点和AAA结构域中存在的残基很重要。本研究揭示了在所有四种血清型中高度保守的具有活性位点残基的肽段。NS3序列的这些区域可能有助于开发抗病毒药物。
