以寨卡病毒NS3解旋酶为靶点的海洋天然产物库的虚拟筛选与成药性评价

Virtual screening and druggability prediction of marine natural product library targeted by NS3 helicase of Zika virus

寨卡病毒病自2015年在巴西等南美洲国家爆发后,已成为影响全球公共卫生的重大问题,但至今仍无可用于治疗该病的获批特效药.运用基于结构的药物虚拟筛选技术,以寨卡病毒NS3解旋酶的2个最新报道的结合位点为口袋,通过海洋天然产物库进行分子对接,初步得到divanchrobactin、bromophenol、2-hydroxy-1′-methylzeatin、garveatin E、aromatic polyketides、dimeric terrestrols等10个化合物,它们能很好地靶向寨卡病毒NS3解旋酶,从而可能成为对寨卡病毒病具有潜在治疗作用的海洋天然产物.同时,利用薛定谔软件套装中的ADMET预测模块对结合较好的化合物展开初步的成药性评价,发现除Divanchrobactin有较严重的成药性问题外,其他化合物均满足药物开发的基本要求,这为后期的实验研究提供了理论基础.

Since the outbreak of Zika virus disease in Brazil and other countries of South America in 2015,it has become a concerned issue affecting the global public health,but so far there is still no approved drug to treat Zika virus disease.According to two newly reported binding sites of NS3 helicase of the Zika virus,we established a library of marine natural products for molecular docking by structure-based virtual screening technology.Virtual screening results showed that 10 compounds including divanchrobactin,bromophenol,2-hydroxy-1′-methylzeatin,garveatin E,aromatic polyketides,dimeric terrestrols,etc.could have good binding patterns towards NS3 helicase and hence could be developed as potential marine natural products for therapy of Zika virus disease.Meanwhile,the ADMET prediction module in the Schrodinger software set was used to carry out a preliminary evaluation of the druggability of the selected compounds with good binding ability,and it was found that all the compounds could satisfy the basic requirements of drug property except for divanchrobactin.Our study provides a theoretical basis for further experimental verification.