Hossain Md Shohel, Hasnat Soharth, Akter Shilpy, Mim Maria Mulla, Tahcin Anika, Hoque Majedul, Sutradhar Durjoy, Keya Mst Alifa Akter, Sium Namin Rouf, Hossain Sophia, Masuma Runa, Rakib Sakhawat Hossen, Islam Md Aminul, Islam Tofazzal, Bhattacharya Prosun, Hoque M Nazmul
Department of Pharmacy, Jahangirnagar University, Dhaka, Bangladesh.
Molecular Biology and Bioinformatics Laboratory, Department of Gynecology, Obstetrics and Reproductive Health, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
Front Pharmacol. 2024 Oct 15;15:1465827. doi: 10.3389/fphar.2024.1465827. eCollection 2024.
Dengue virus (DENV) infection, spread by mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.
This study aimed to identify inhibitory phytocompounds in (), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.
The chemical structures of 17 compounds from were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.
Among these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski's "rule of 5", showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.
Taken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.
登革病毒（DENV）感染通过蚊子传播，是热带和亚热带地区一个重大的公共卫生问题。在DENV的四种不同血清型（DENV-1至DENV-4）中，DENV-2在全球导致的死亡人数最多。然而，对于由DENV-2引起的登革热患者，目前尚无特效治疗方法。
本研究旨在鉴定一种广泛使用的传统药用植物（此处原文括号内容缺失）中的抑制性植物化合物，用于治疗与DENV-2相关的疾病。
从《印度药用植物、植物化学与治疗学》（IMPPAT）数据库获取了该植物中17种化合物的化学结构。这些化合物进行了几何优化，针对DENV-2的非结构蛋白1（NSP1）进行筛选，并通过分子动力学模拟（MDS）进一步验证。黄芩素是一种已证实的抗DENV-2药物，用于分子筛选、MDS和MM-GBSA分析中的验证。
在这些化合物中，β-香树脂醇、β-香树脂醇乙酸酯、 Chrysoeriol、异荭草素和木犀草素显示出作为DENV-2的NSP1抑制剂的潜在前景，热力学性质、分子轨道、静电势、光谱数据和分子筛选结果均支持这一点。此外，这些化合物符合Lipinski的“五规则”，无肝毒性/细胞毒性，但有混合的致突变性、免疫毒性和致癌性。此外，通过MDS的最终验证证实了它们的潜力，显示出稳定的趋势，对DENV-2的NSP1的抑制活性明显高于对照药物黄芩素。在筛选出化合物中，Chrysoeriol成为DENV-2的NSP1最有前景的抑制剂，其次是木犀草素和异荭草素。
综上所述，我们的结果表明Chrysoeriol是DENV-2的NSP1的最佳抑制剂，可作为治疗和管理DENV-2感染的治疗剂或先导化合物进行评估。
