Sharifi Amirhossein, Amanlou Arash, Moosavi-Movahedi Faezeh, Golestanian Sahand, Amanlou Massoud
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 16 Azar Ave., Tehran, Iran.
Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Comput Biol Chem. 2017 Oct;70:1-6. doi: 10.1016/j.compbiolchem.2017.06.003. Epub 2017 Jul 1.
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is one of the deadliest human diseases with mortality rate near 50%. Special attention should be paid to this virus since there is no approved treatment for it. On the other hand, the recent outbreak of Ebola virus which is a member of hemorrhagic fever viruses shows this group of viruses can be extremely dangerous. Previous studies have indicated that nucleoprotein of CCHFV, a pivotal protein in virus replication, is an appropriate target for antiviral drug development. The aim of this study is finding inhibitor(s) of this protein. Herein, a virtual screening procedure employing docking followed by molecular dynamic was used to identify small molecule inhibitors of the nucleoprotein from FDA-approved drugs. Regarding CCHFV, using in-silico method is a safe way to achieve its inhibitor(s) since this virus is categorized as a World Health Organization (WHO) biosafety level 4 pathogen and therefore investigation in general laboratories is restricted. In conclusion, considering docking and molecular dynamic results alongside with bioavailability of FDA-approved drugs, doxycycline and minocycline are proposed as potential inhibitors of CCHFV nucleoprotein. There is hope, this study encourage other research groups for in-vitro and in-vivo studies about the efficacy of those two medicines in CCHFV treatment.
克里米亚-刚果出血热病毒(CCHFV)是最致命的人类疾病之一,死亡率接近50%。鉴于目前尚无针对该病毒的获批治疗方法,因此应特别关注这种病毒。另一方面,最近作为出血热病毒成员之一的埃博拉病毒爆发表明,这组病毒可能极其危险。先前的研究表明,CCHFV的核蛋白是病毒复制中的关键蛋白,是抗病毒药物开发的合适靶点。本研究的目的是寻找该蛋白的抑制剂。在此,采用对接随后进行分子动力学的虚拟筛选程序,从FDA批准的药物中鉴定核蛋白的小分子抑制剂。对于CCHFV,使用计算机模拟方法是获得其抑制剂的安全途径,因为这种病毒被归类为世界卫生组织(WHO)生物安全4级病原体,因此在普通实验室进行研究受到限制。总之,综合对接和分子动力学结果以及FDA批准药物的生物利用度,强力霉素和米诺环素被提议作为CCHFV核蛋白的潜在抑制剂。令人期待的是,本研究鼓励其他研究小组对这两种药物在CCHFV治疗中的疗效进行体外和体内研究。