Yang Siyun, Kar Supratik
Chemometrics and Molecular Modeling Laboratory, Department of Chemistry, Kean University, 1000 Morris Avenue, Union, NJ 07083 USA.
Struct Chem. 2023 Mar 8:1-19. doi: 10.1007/s11224-023-02148-6.
Nipah virus (NiV) is a high-lethality RNA virus from the family of and genus , classified under Biosafety Level-4 (BSL-4) pathogen due to the severity of pathogenicity and lack of medications and vaccines. Direct contacts or the body fluids of infected animals are the major factor of transmission of NiV. As it is not an airborne infection, the transmission rate is relatively low. Still, mutations of the NiV in the animal reservoir over the years, followed by zoonotic transfer, can make the deadliness of the virus manifold in upcoming years. Therefore, there is no denial of the possibility of a pandemic after COVID-19 considering the severe pathogenicity of NiV, and that is why we need to be prepared with possible drugs in upcoming days. Considering the time constraints, computational aided drug design (CADD) is an efficient way to study the virus and perform the drug design and test the HITs to lead experimentally. Therefore, this review focuses primarily on NiV target proteins (covering NiV and human), experimentally tested repurposed drug details, and latest computational studies on potential lead molecules, which can be explored as potential drug candidates. Computationally identified drug candidates, including their chemical structures, docking scores, amino acid level interaction with corresponding protein, and the platform used for the studies, are thoroughly discussed. The review will offer a one-stop study to access what had been performed and what can be performed in the CADD of NiV.
尼帕病毒(NiV)是一种来自 科 属的高致死性RNA病毒,由于其致病性严重且缺乏药物和疫苗,被归类为生物安全4级(BSL-4)病原体。直接接触或感染动物的体液是尼帕病毒传播的主要因素。由于它不是空气传播感染,传播率相对较低。然而,多年来动物宿主中尼帕病毒的突变,随后的人畜共患病传播,可能会使该病毒在未来几年的致死性增加数倍。因此,考虑到尼帕病毒的严重致病性,在新冠疫情之后不能排除大流行的可能性,这就是为什么我们需要在未来几天准备好可能的药物。考虑到时间限制,计算机辅助药物设计(CADD)是研究该病毒、进行药物设计并通过实验测试命中化合物以获得先导物的有效方法。因此,本综述主要关注尼帕病毒的靶蛋白(涵盖尼帕病毒和人类)、经过实验测试的药物再利用细节以及关于潜在先导分子的最新计算研究,这些分子可作为潜在的药物候选物进行探索。文中对通过计算确定的药物候选物进行了全面讨论,包括它们的化学结构、对接分数、与相应蛋白质的氨基酸水平相互作用以及用于研究的平台。本综述将提供一站式研究,以了解在尼帕病毒的计算机辅助药物设计中已经做了什么以及可以做什么。