从巴基斯坦临床分离的登革病毒非结构蛋白中鉴定新的抗病毒靶点的分子和结构见解

IF 2.7 4区医学 Q3 VIROLOGY

Virus research Pub Date : 2025-10-03 DOI:10.1016/j.virusres.2025.199637

Liaqat Ali , Nida Kanwal , Iffat Saleem , Haidar Ali , Deeba Amraiz , Madiha Akram , Imran Shahid , Jing Yang

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引用次数: 0

摘要

登革热病毒（DENV）仍然是全球健康威胁，巴基斯坦正在经历反复暴发，但对病毒复制和发病机制至关重要的非结构基因（NS1、NS2A、NS5）在当地菌株中的研究仍不足。本研究通过巢式PCR、Sanger测序和系统发育工具（MEGA11）分析了150份NS1阳性血清样本（2022-2024），发现DENV-2为优势血清型（85%的样本），其中NS5与印度/Swat菌株具有97%的同源性，而NS1和NS2A在功能域上存在序列差异。计算机建模和对接研究发现，RK-0404678与NS5 （-6.4 kcal/mol）和Galidesivir与NS5 （-7.2 kcal/mol）具有很强的结合，表明它们具有抗病毒候选药物的潜力。这些发现强调了DENV-2在巴基斯坦的优势地位，并确定了NS5的保守区域是有希望的药物靶点，尽管需要进一步的实验验证。

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Molecular and structural insights into dengue virus non-structural proteins from pakistani clinical isolates for the identification of novel antiviral targets

Dengue virus (DENV) remains a global health threat, with Pakistan experiencing recurrent outbreaks, yet non-structural genes (NS1, NS2A, NS5) critical for viral replication and pathogenesis remain understudied in local strains. In this study, 150 NS1-positive serum samples (2022–2024) were analyzed via nested PCR, Sanger sequencing, and phylogenetic tools (MEGA11), revealing DENV-2 as the dominant serotype (85 % of samples), with NS5 showing 97 % homology to Indian/Swat strains, while NS1 and NS2A exhibited sequence variation in functional domains. In silico modeling and docking studies identified RK-0404,678 as a strong binder to NS5 (−6.4 kcal/mol) and Galidesivir to NS5 (−7.2 kcal/mol), suggesting their potential as antiviral candidates. These findings highlight DENV-2 dominance in Pakistan and identify conserved regions in NS5 as promising drug targets, though further experimental validation is warranted.

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来源期刊

Virus research 医学-病毒学

CiteScore

9.50

自引率

2.00%

发文量

239

审稿时长

43 days

期刊介绍： Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.