Jayaswal Amit, Mishra Hirdyesh, Mishra Ankita, Shah Kavita
Bioinformatics Section, Mahila Maha Vidyalaya, Banaras Hindu University, Varanasi, 221005, India.
Department of Physics, Mahila Maha Vidyalaya, Banaras Hindu University, Varanasi, 221005, India.
Arch Virol. 2019 Apr;164(4):949-960. doi: 10.1007/s00705-019-04153-9. Epub 2019 Jan 24.
HIV is one of the most lethal viral diseases in the human population. Patients often suffer from drug resistance, which hampers HIV therapy. Eleven different structural analogues of saquinavir (SQV), designed using ChemSketch™ and named S1 through S11, were compared with SQV with respect to their pharmacodynamic and pharmacokinetic properties. Pharmacokinetic predictions were carried out using AutoDock, and molecular docking between macromolecule HIV protease (PDB ID: 3IXO) and analogues S1 - S11 as ligands was performed. Analogues S1, S3, S4, S9 and S11 had lower binding scores when compared with saquinavir, whereas that of analogue S5 was similar. Pharmacokinetic predictions made using ACDilab2, including the Lipinski profile, general physical features, absorption, distribution, metabolism and excretion parameters, and toxicity values, for the eleven analogues and SQV suggested that S1 and S5 are pharmacodynamically and pharmacokinetically robust molecules that could be developed and established as lead molecules after in vitro and in vivo studies.
人类免疫缺陷病毒（HIV）是人类最致命的病毒性疾病之一。患者常出现耐药性，这阻碍了HIV治疗。使用ChemSketch™设计了11种不同的沙奎那韦（SQV）结构类似物，命名为S1至S11，并将它们与沙奎那韦在药效学和药代动力学特性方面进行了比较。使用AutoDock进行药代动力学预测，并进行了大分子HIV蛋白酶（PDB ID：3IXO）与作为配体的类似物S1 - S11之间的分子对接。与沙奎那韦相比，类似物S1、S3、S4、S9和S11的结合分数较低，而类似物S5的结合分数与之相似。使用ACDilab2对这11种类似物和沙奎那韦进行的药代动力学预测，包括Lipinski参数、一般物理特性、吸收、分布、代谢和排泄参数以及毒性值，表明S1和S5是药效学和药代动力学方面稳定的分子，经过体外和体内研究后可开发并确立为先导分子。
