Dwivedi Vivek Dhar, Tripathi Indra Prasad, Mishra Sarad Kumar
Faculty of Science and Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, Satna, Madhya Pradesh; Department of Biotechnology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, Uttar Pradesh, India.
Faculty of Science and Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, Satna, Madhya Pradesh, India.
J Vector Borne Dis. 2016 Apr-Jun;53(2):156-61.
BACKGROUND & OBJECTIVES: NS2B-NS3 protease (NS2B-NS3 pro ) of dengue virus (DENV) is the prime therapeutic target for the development of anti-dengue drug to combat the DENV infection, which is currently an increasing health problem in many countries. In the area of antiviral drug discovery, numerous reports on the antiviral activity of various medicinal plants against dengue viruses have been published. Neem plant (Azadirachta indica) is one among those medicinal plants which is reported to show potential antiviral activity against DENV. But active principle of neem plant extract which has inhibitory potential against DENV NS2B-NS3 pro is not yet reported. The aim of the present study was to explore the inhibitory potential of five triterpenoids from neem plant, viz. nimbin, desacetylnimbin, desacetylsalannin, azadirachtin and salannin, against DENV NS2B-NS3 pro.
The molecular 3D structural data of DENV NS2B-NS3 pro and selected triterpenoids of neem plant were collected from protein databank (PDB ID: 2VBC) and PubChem database respectively. The molecular docking approach was employed to find out the in silico inhibitory potential of the five triterpenoids against DENV NS2B- NS3 pro.
The molecular docking results showed that nimbin, desacetylnimbin and desacetylsalannin have good binding affinity with DENV NS2B-NS3 pro , while azadirachtin and salannin did not show any interaction with the target protein. It was observed that the DENV NS2B-NS3 pro binding energy for nimbin, desacetylnimbin and desacetylsalannin were -5.56, -5.24 and -3.43 kcal/mol, respectively.
INTERPRETATION & CONCLUSION: The findings attained through this study on the molecular interaction mode of three neem triterpenoids and DENV NS2B-NS3 pro can be considered for further in vitro and in vivo validation for designing new potential drugs for DENV infection.
登革病毒（DENV）的NS2B - NS3蛋白酶（NS2B - NS3 pro）是开发抗登革病毒药物以对抗DENV感染的主要治疗靶点，目前在许多国家，DENV感染已成为日益严重的健康问题。在抗病毒药物研发领域，已发表了众多关于各种药用植物对登革病毒抗病毒活性的报道。印楝植物（Azadirachta indica）是其中据报道对DENV具有潜在抗病毒活性的药用植物之一。但尚未报道印楝植物提取物中对DENV NS2B - NS3 pro具有抑制潜力的活性成分。本研究的目的是探索印楝植物中的五种三萜类化合物，即尼姆宾、去乙酰尼姆宾、去乙酰萨兰宁、印楝素和萨兰宁对DENV NS2B - NS3 pro的抑制潜力。
分别从蛋白质数据库（PDB ID：2VBC）和PubChem数据库收集DENV NS2B - NS3 pro和印楝植物所选三萜类化合物的分子三维结构数据。采用分子对接方法来研究这五种三萜类化合物对DENV NS2B - NS3 pro的计算机模拟抑制潜力。
分子对接结果表明，尼姆宾、去乙酰尼姆宾和去乙酰萨兰宁与DENV NS2B - NS3 pro具有良好的结合亲和力，而印楝素和萨兰宁与靶蛋白未显示任何相互作用。观察到尼姆宾、去乙酰尼姆宾和去乙酰萨兰宁与DENV NS2B - NS3 pro的结合能分别为 - 5.56、 - 5.24和 - 3.43千卡/摩尔。
本研究通过对三种印楝三萜类化合物与DENV NS2B - NS3 pro分子相互作用模式的研究结果，可考虑进一步进行体外和体内验证，以设计针对DENV感染的新型潜在药物。
