Saha Otun, Siddiquee Noimul Hasan, Akter Rahima, Sarker Nikkon, Bristi Uditi Paul, Sultana Khandokar Fahmida, Remon Sm Lutfor Rahman, Sultana Afroza, Shishir Tushar Ahmed, Rahaman Md Mizanur, Ahmed Firoz, Hossen Foysal, Amin Mohammad Ruhul, Akter Mir Salma
Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh.
Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh.
Bioinform Biol Insights. 2024 Jul 27;18:11779322241264145. doi: 10.1177/11779322241264145. eCollection 2024.
The Nipah virus (NiV) belongs to the genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant () from the IMPPAT database, and molecular docking was used to ascertain the compounds' binding strength. The top 3 phytochemicals with binding affinities of -7.118, -7.074, and -6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was -47.56, -47.3, and -43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.
尼帕病毒（NiV）属于 属，是一个严重的公共卫生问题，引发了众多致死率较高的疫情爆发。不幸的是，目前尚无针对尼帕病毒的有效药物。为了研究可能的尼帕病毒感染抑制剂，我们在这项工作中使用计算机技术来发现治疗候选药物。由于目前尚无针对尼帕病毒感染的获批治疗方法，我们将尼帕病毒包膜附着糖蛋白作为研究靶点，该蛋白负责与宿主细胞结合并进入宿主细胞。我们的计算机辅助药物设计方法包括分子对接、对接后分子机制广义Born表面积（MM - GBSA）、吸收、分布、代谢、排泄/毒性（ADME/T）以及分子动力学（MD）模拟。我们从IMPPAT数据库中检索了418种与印楝植物（）相关的植物化学物质，并使用分子对接来确定这些化合物的结合强度。根据分子对接结果，分别选择了CID为5280343、9064和5280863的结合亲和力为 -7.118、-7.074和 -6.894 kcal/mol的前3种植物化学物质进行进一步研究。这3种化合物对接后的MM - GBSA分别为 -47.56、-47.3和 -43.15 kcal/mol。作为其有效性和安全性的证据，所有选定药物均具有良好的毒理学和药代动力学（Pk）特性。我们还进行了MD模拟，以确认配体 - 蛋白质复合物结构的稳定性，并确定所选化合物在蛋白质结合位点是否稳定。根据分子对接、MM - GBSA和MD模拟结果，所有3种植物化学物质，槲皮素（CID：5280343）、花旗松素（CID：9064）和山奈酚（CID：5280863），与对照药物利巴韦林相比，似乎对靶蛋白具有出色的结合稳定性。总体而言，这项工作为开发治疗尼帕病毒感染的新型药物提供了一种可行的方法。
