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针对裂谷热病毒帽结合结构域的植物化学抑制剂的计算预测

Computational prediction of phytochemical inhibitors against the cap-binding domain of Rift Valley fever virus.

作者信息

Muralitharan Ishwarya, Sahoo Ajaya Kumar, Augusthian Priya Dharshini, Samal Areejit

机构信息

Computational Biology Group, The Institute of Mathematical Sciences (IMSc), CIT Campus, Taramani, Chennai, 600113, India.

Homi Bhabha National Institute (HBNI), Mumbai, 400094, India.

出版信息

Mol Divers. 2024 Aug;28(4):2637-2650. doi: 10.1007/s11030-023-10702-x. Epub 2023 Jul 23.

Abstract

Rift Valley fever is a zoonotic disease that can spread through livestock and mosquitoes, and its symptoms include retinitis, photophobia, hemorrhagic fever and neurological effects. The World Health Organization has identified Rift Valley fever as one of the viral infections that has potential to cause a future epidemic. Hence, efforts are urgently needed toward development of therapeutics and vaccine against this infectious disease. Notably, the causative virus namely, the Rift Valley fever virus (RVFV), utilizes the cap-snatching mechanism for viral transcription, rendering its cap-binding domain (CBD) as an effective antiviral target. To date, there are no published studies towards identification of potential small molecule inhibitors for the CBD of RVFV. Here, we employ a virtual screening workflow comprising of molecular docking and molecular dynamics (MD) simulation, to identify 5 potential phytochemical inhibitors of the CBD of RVFV. These 5 phytochemical inhibitors can be sourced from Indian medicinal plants, Ferula assa-foetida, Glycyrrhiza glabra and Leucas cephalotes, used in traditional medicine. In sum, the 5 phytochemical inhibitors of the CBD of RVFV identified by this purely computational study are promising drug lead molecules which can be considered for detailed experimental validation against RVFV infection.

摘要

裂谷热是一种人畜共患病,可通过家畜和蚊子传播,其症状包括视网膜炎、畏光、出血热和神经效应。世界卫生组织已将裂谷热确定为有可能在未来引发疫情的病毒感染之一。因此,迫切需要努力开发针对这种传染病的治疗方法和疫苗。值得注意的是,致病病毒即裂谷热病毒(RVFV)利用抢帽机制进行病毒转录,使其帽结合结构域(CBD)成为一个有效的抗病毒靶点。迄今为止,尚未有关于鉴定RVFV的CBD潜在小分子抑制剂的公开研究。在此,我们采用了一种包括分子对接和分子动力学(MD)模拟的虚拟筛选工作流程,以鉴定5种RVFV的CBD潜在植物化学抑制剂。这5种植物化学抑制剂可从印度药用植物阿魏、光果甘草和头花卢卡斯中提取,这些植物用于传统医学。总之,通过这项纯计算研究鉴定出的5种RVFV的CBD植物化学抑制剂是有前景的药物先导分子,可考虑针对RVFV感染进行详细的实验验证。

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