School of Biotechnology and Bioinformatics, D.Y. Patil Deemed to be University, CBD Belapur, Navi Mumbai, India.
Department of Biotechnology, St. Xavier's College, Mumbai, India.
J Biomol Struct Dyn. 2024 Nov;42(18):9388-9398. doi: 10.1080/07391102.2023.2252084. Epub 2023 Aug 29.
The infectious Nipah virus (NiV) is categorized into NiV-M (Malaysia) and NiV-B (Bangladesh) groups based on its genome comparison, pathogenicity, and mortality rate. The development of therapeutic molecules has used NiV-M-derived data in multiple studies than NiV-B. In continuation with this, the protein level investigation is also less explored to understand the interaction with therapeutic neutralizing antibodies for NiV-B. So, this study focuses on understanding the impact of NiV-B-specific mutations on the interaction of therapeutic neutralizing antibodies with the G protein. The population-based comparative analysis of NiV-B G protein sequences with NiV-M sequence identified twenty-six mutations. These predominantly polar mutations were then used to model the mutant protein (G_MT). In a comparative study, the G protein G_MT and reference protein G_WT (Malaysian origin) were subjected to a protein docking with neutralizing human monoclonal antibody HENV26. The binding affinity and the free binding energy of the glycoprotein in complex with G-WT and G_MT were calculated using PRODIGY and MM/PBSA tools respectively. Based on the PRODIGY report, G-WT showed stronger binding (-13.8 kcal/mol) compared to that of the G_MT (-9.0 kcal/mol) with the HENV26 antibody. The stability of the complexes was evaluated using MM/PBSA which showed higher binding energy with HENV26 for G_WT (-75.11 kcal/mol) in contrast to G_MT (-41.66 kcal/mol). The results indicate that the mutant G protein has a reduced ability to bind to neutralizing antibodies, resulting in a decreased effectiveness against strains carrying these mutations.Communicated by Ramaswamy H. Sarma.
基于基因组比较、致病性和死亡率，传染性尼帕病毒（NiV）被分为 NiV-M（马来西亚）和 NiV-B（孟加拉国）两个组。在多项研究中，使用 NiV-M 衍生数据开发治疗性分子的情况多于 NiV-B。在此基础上，对于 NiV-B 与治疗性中和抗体相互作用的蛋白质水平研究也较少。因此，本研究侧重于了解 NiV-B 特异性突变对治疗性中和抗体与 G 蛋白相互作用的影响。对 NiV-B G 蛋白序列与 NiV-M 序列进行基于人群的比较分析，确定了 26 个突变。然后，这些主要的极性突变被用于构建突变蛋白（G_MT）模型。在一项比较研究中，将 G 蛋白 G_MT 和参考蛋白 G_WT（马来西亚起源）与中和人单克隆抗体 HENV26 进行蛋白对接。使用 PRODIGY 和 MM/PBSA 工具分别计算糖蛋白与 G-WT 和 G_MT 复合物的结合亲和力和自由结合能。根据 PRODIGY 报告，G-WT 与 HENV26 抗体的结合强度（-13.8 kcal/mol）强于 G_MT（-9.0 kcal/mol）。使用 MM/PBSA 评估复合物的稳定性，结果表明 G_WT 与 HENV26 的结合能更高（-75.11 kcal/mol），而 G_MT 则较低（-41.66 kcal/mol）。结果表明，突变的 G 蛋白与中和抗体的结合能力降低，从而降低了对携带这些突变的病毒株的有效性。通讯作者为 Ramaswamy H. Sarma。
