Gopikrishnan Mohanraj, Elavarasu Santhosh Mudipalli, Vasudevan Karthick, Shree Devi M S, K Sasikumar, Varsha A Shree Laya, Doss C George Priya
Department of Integrative Biology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India.
Manipal Academy of Higher Education (MAHE), Manipal, 576104, India; Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India.
Comput Biol Med. 2025 May;190:109973. doi: 10.1016/j.compbiomed.2025.109973. Epub 2025 Apr 1.
Nipah virus (NiV) is a highly contagious zoonotic pathogen causing severe encephalitis and respiratory illnesses in humans. With a high fatality rate and no FDA-approved treatments, NiV poses a significant public health threat. This study conducts a comprehensive Bayesian phylogenetic analysis of all publicly available NiV genomes since the first human case. Additionally, a protein-protein interaction (PPI) network analysis focusing on Pteropus species was performed to identify potential therapeutic targets. High-throughput virtual screening assessed the inhibitory potential of Kabasura Kudineer Chooranam phytocompounds against these targets. Molecular dynamic simulations (MDS) were conducted to evaluate the stability and dynamic characteristics of NiV proteins bound to specific inhibitors. Bayesian phylogenetic analysis of 280 NiV genomes revealed two distinct clades among Indian isolates, highlighting significant regional diversity. Notably, the latest strain, OM135495, along with other NiV variants in Kerala, underscores the virus's rapid genetic evolution since 2015. The PPI network identified NiV-F, NiV-G, and NiV-N as key therapeutic targets. Among the tested phyto compounds, Vasicinone and Piperine exhibited strong binding affinities (-4.51 to -5.96 kcal/mol) and enhanced stability during MDS, suggesting their potential as antiviral agents. These findings indicate that phyto compounds may serve as viable alternatives for NiV treatment, paving the way for novel drug development. However, further validation through laboratory and animal studies is essential. This study enhances our understanding of NiV evolution, informs public health strategies, and contributes to preparedness for future outbreaks.
尼帕病毒（NiV）是一种极具传染性的人畜共患病原体，可导致人类严重的脑炎和呼吸道疾病。由于病死率高且没有获得美国食品药品监督管理局（FDA）批准的治疗方法，尼帕病毒对公众健康构成了重大威胁。本研究对自首例人类病例以来所有公开可用的尼帕病毒基因组进行了全面的贝叶斯系统发育分析。此外，还进行了一项针对狐蝠属物种的蛋白质-蛋白质相互作用（PPI）网络分析，以确定潜在的治疗靶点。高通量虚拟筛选评估了卡巴萨拉库迪内尔丸植物化合物对这些靶点的抑制潜力。进行了分子动力学模拟（MDS），以评估与特定抑制剂结合的尼帕病毒蛋白的稳定性和动态特征。对280个尼帕病毒基因组的贝叶斯系统发育分析揭示了印度分离株中的两个不同进化枝，突出了显著的区域多样性。值得注意的是，最新毒株OM135495以及喀拉拉邦的其他尼帕病毒变体，突显了该病毒自2015年以来的快速基因进化。PPI网络确定尼帕病毒F蛋白、尼帕病毒G蛋白和尼帕病毒N蛋白为关键治疗靶点。在所测试的植物化合物中，瓦西酮和胡椒碱表现出很强的结合亲和力（-4.51至-5.96千卡/摩尔），并且在MDS过程中稳定性增强，表明它们具有作为抗病毒药物的潜力。这些发现表明，植物化合物可能成为治疗尼帕病毒的可行替代方案，为新型药物开发铺平了道路。然而，通过实验室和动物研究进行进一步验证至关重要。本研究增进了我们对尼帕病毒进化的理解，为公共卫生策略提供了信息，并有助于为未来疫情爆发做好准备。
