Gul Fizza, Ahmad Sajjad, Khan Kalsoom, Masood Rehana, Siddique Farhan, Bibi Mehvish, Aljahdali Salma Mohammed, Aljasir Mohammad Abdullah, Jassim Tabarak Sabah, Wei Dong-Qing, Irfan Muhammad
Department of Health and Biological Sciences, Abasyn University, Peshawar, 25000, Pakistan.
Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Nayang, 473006, People's Republic of China.
Mol Biotechnol. 2024 Dec 6. doi: 10.1007/s12033-024-01326-z.
Alongshan virus (ALSV) is a novel tick-borne virus associated with human diseases. The ALSV is a segmented flavivirus from the family Flaviviridae. It is currently considered as tick-borne arbovirus. There is a high incidence of fever and headache among patients with ALSV infection, and some patients also present with fatigue, coma, depression, nausea, myalgia/arthralgia, and skin rashes. Neither a licensed vaccine nor a drug is currently available to treat ALSV. The development of new, practical, and innovative therapeutic approaches is needed to overcome the emergence of the pathogen. Research on drugs remains a complex, time-consuming, and expensive. The field of drug development has undergone a revolution due to the use of computational approaches, which provide several benefits that speed up and improve the process of developing novel drugs. The goal of this study is to identify novel drug-like molecules against NS3-like helicase enzyme of Alongshan virus. Using molecular docking, the binding potential of the top three ligands to the specified target was determined. Molecular dynamic simulations were used to identify the stabilities of the best-docked conformations followed by energy calculations and ADMET analysis. Three potential and promising compounds were identified by performing structure-based virtual screening of non-structural protein 3 (NS3) like helicase of Alongshan virus. The best-docked complexes identified through virtual screening were BDC-23169381, BDB-26412846, BDB-2641954. All these compounds had good pharmacokinetics characteristics and were identified as drug like.
阿龙山病毒（ALSV）是一种与人类疾病相关的新型蜱传病毒。阿龙山病毒是黄病毒科的一种分节段黄病毒。目前它被认为是蜱传虫媒病毒。阿龙山病毒感染患者中发热和头痛的发生率较高，一些患者还出现疲劳、昏迷、抑郁、恶心、肌痛/关节痛和皮疹。目前尚无用于治疗阿龙山病毒的许可疫苗或药物。需要开发新的、实用的和创新的治疗方法来应对这种病原体的出现。药物研究仍然复杂、耗时且昂贵。由于计算方法的应用，药物开发领域经历了一场革命，这些方法提供了多项益处，可加速并改进新型药物的开发过程。本研究的目的是鉴定针对阿龙山病毒NS3样解旋酶的新型类药物分子。通过分子对接，确定了排名前三的配体与指定靶点的结合潜力。利用分子动力学模拟来确定最佳对接构象的稳定性，随后进行能量计算和药物代谢及毒性预测分析。通过对阿龙山病毒非结构蛋白3（NS3）样解旋酶进行基于结构的虚拟筛选，鉴定出三种有潜力且有前景的化合物。通过虚拟筛选确定的最佳对接复合物为BDC - 23169381、BDB - 26412846、BDB - 2641954。所有这些化合物都具有良好的药代动力学特征，并被鉴定为类药物。
