In silico investigation and identification of potential phytocompounds targeting dengue virus NS5 methyltransferase.

In silico pharmacology Pub Date : 2026-09-14 eCollection Date: 2026-01-01 DOI:10.1007/s40203-026-00723-3

Sumiya Ahmad Sejuti, Mijan Mia, Apurbo Pal, Ahsan Habib

{"title":"In silico investigation and identification of potential phytocompounds targeting dengue virus NS5 methyltransferase.","authors":"Sumiya Ahmad Sejuti, Mijan Mia, Apurbo Pal, Ahsan Habib","doi":"10.1007/s40203-026-00723-3","DOIUrl":null,"url":null,"abstract":"Dengue is an escalating public health threat in warm climate zones, particularly in tropical and subtropical regions. The World Health Organization (WHO) recorded approximately 4 million cases and 3000 deaths in 97 countries between January and July 2025, highlighting the urgent need for effective antiviral therapeutics. The presence of four genetically distinct serotypes of dengue virus (DENV) and the lack of a broadly effective drug pose major challenges for disease control. This study utilized an in silico approach to suggest potential phytocompounds targeting the non-structural protein 5 (NS5) methyltransferase, a crucial protein involved in 5'-mRNA capping. A total of 605 phytocompounds from Allium sativum, Curcuma longa, Camellia sinensis, and Carica papaya were screened based on Lipinski's rule of five and docked against the NS5 methyltransferase protein. Eight compounds exhibited higher predicted binding affinities than the control (-7.648 kcal/mol) with Dehydrocarpaine-I showing the most favorable predicted binding affinities (-9.456 kcal/mol). Top candidates were further evaluated based on their pharmacokinetic properties, toxicity profiles, and the protein-ligand interactions. Molecular dynamics simulations and principal component analysis (PCA) suggested the stability and favorable dynamic behavior of Dehydrocarpaine-I, Theasapogenol-B, and Brassinolide. MM-PBSA calculations showed that Theasapogenol-B (-62.48 kcal/mol) and Brassinolide (-44.82 kcal/mol) exhibited more favorable binding free energies compared to the control (-43.46 kcal/mol). This study suggests Theasapogenol-B and Brassinolide as potential lead compounds targeting NS5 methyltransferase and provides a basis for further comprehensive in silico, in vitro and in vivo validation.Graphical abstract: Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00723-3.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"236"},"PeriodicalIF":0.0000,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575057/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In silico pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40203-026-00723-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Dengue is an escalating public health threat in warm climate zones, particularly in tropical and subtropical regions. The World Health Organization (WHO) recorded approximately 4 million cases and 3000 deaths in 97 countries between January and July 2025, highlighting the urgent need for effective antiviral therapeutics. The presence of four genetically distinct serotypes of dengue virus (DENV) and the lack of a broadly effective drug pose major challenges for disease control. This study utilized an in silico approach to suggest potential phytocompounds targeting the non-structural protein 5 (NS5) methyltransferase, a crucial protein involved in 5'-mRNA capping. A total of 605 phytocompounds from Allium sativum, Curcuma longa, Camellia sinensis, and Carica papaya were screened based on Lipinski's rule of five and docked against the NS5 methyltransferase protein. Eight compounds exhibited higher predicted binding affinities than the control (-7.648 kcal/mol) with Dehydrocarpaine-I showing the most favorable predicted binding affinities (-9.456 kcal/mol). Top candidates were further evaluated based on their pharmacokinetic properties, toxicity profiles, and the protein-ligand interactions. Molecular dynamics simulations and principal component analysis (PCA) suggested the stability and favorable dynamic behavior of Dehydrocarpaine-I, Theasapogenol-B, and Brassinolide. MM-PBSA calculations showed that Theasapogenol-B (-62.48 kcal/mol) and Brassinolide (-44.82 kcal/mol) exhibited more favorable binding free energies compared to the control (-43.46 kcal/mol). This study suggests Theasapogenol-B and Brassinolide as potential lead compounds targeting NS5 methyltransferase and provides a basis for further comprehensive in silico, in vitro and in vivo validation.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00723-3.

查看原文本刊更多论文

针对登革病毒NS5甲基转移酶的潜在植物化合物的计算机研究和鉴定。

登革热是温暖气候地区，特别是热带和亚热带地区不断升级的公共卫生威胁。根据世界卫生组织（世卫组织）的记录，2025年1月至7月期间，97个国家约有400万例病例和3000人死亡，突出表明迫切需要有效的抗病毒治疗方法。登革热病毒（DENV）的四种基因上不同的血清型的存在以及缺乏广泛有效的药物对疾病控制构成了重大挑战。本研究利用计算机方法提出了针对非结构蛋白5 （NS5）甲基转移酶的潜在植物化合物，NS5甲基转移酶是参与5'-mRNA capping的关键蛋白。从葱、姜黄、山茶和番木瓜中筛选出605个化合物，并与NS5甲基转移酶蛋白对接。8个化合物的预测结合亲和度均高于对照（-7.648 kcal/mol），其中dehydrocarpaini的预测结合亲和度最高（-9.456 kcal/mol）。根据它们的药代动力学特性、毒性特征和蛋白质与配体的相互作用，进一步评估最佳候选药物。分子动力学模拟和主成分分析（PCA）表明，脱氢油碱- 1、茶皂素- b和油菜素内酯具有良好的稳定性和动力学行为。MM-PBSA计算结果表明，茶素醇b （-62.48 kcal/mol）和油菜素内酯（-44.82 kcal/mol）的结合自由能优于对照（-43.46 kcal/mol）。本研究提示茶apogenol- b和油菜素内酯可能是靶向NS5甲基转移酶的先导化合物，为进一步全面的体内、体外验证奠定了基础。图片摘要：补充信息：在线版本包含补充材料，可在https://doi.org/10.1007/s40203-026-00723-3上获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

In silico pharmacology

自引率

0.00%

发文量