Biophysics Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.
Biophysics Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.
Life Sci. 2019 Jan 15;217:176-184. doi: 10.1016/j.lfs.2018.12.004. Epub 2018 Dec 4.
To investigate the efficacy of Direct Acting Antivirals (DAAs) in the treatment of different Hepatitis C Virus (HCV) genotypes.
Homology modeling is used to predict the 3D structures of different genotypes while molecular docking is employed to predict genotype - drug interactions (Binding Mode) and binding free energy (Docking Score).
Simeprevir (TMC435) and to a lesser degree MK6325 are the best drugs among the studied drugs. The predicted affinity of drugs against genotype 1a is always better than other genotypes. P2-P4 macrocyclic drugs show better performance against genotypes 2, 3 and 5. Macrocyclic drugs are better than linear drugs.
HCV is one of the major health problems worldwide. Until the discovery of DAAs, HCV treatment faced many failures. DAAs target key functional machines of the virus life cycle and shut it down. NS3/4A protease is an important target and several drugs have been designed to inhibit its functions. There are several NS3/4A protease drugs approved by Food and Drug Administration (FDA). Unfortunately, the virus exhibits resistance against these drugs. This study is significant in elucidating that no one drug is able to treat different genotypes with the same efficiency. Therefore, treatment should be prescribed based on the HCV genotype.
研究直接作用抗病毒药物（DAAs）治疗不同丙型肝炎病毒（HCV）基因型的疗效。
同源建模用于预测不同基因型的 3D 结构，而分子对接用于预测基因型-药物相互作用（结合模式）和结合自由能（对接评分）。
simeprevir（TMC435）和在较小程度上 MK6325 是研究药物中最好的药物。预测药物对基因型 1a 的亲和力总是优于其他基因型。P2-P4 大环药物对基因型 2、3 和 5 的表现更好。大环药物优于线性药物。
HCV 是全球主要的健康问题之一。直到 DAAs 的发现，HCV 治疗面临许多失败。DAAs 针对病毒生命周期的关键功能机器并将其关闭。NS3/4A 蛋白酶是一个重要的靶标，已经设计了几种药物来抑制其功能。美国食品和药物管理局（FDA）已经批准了几种 NS3/4A 蛋白酶药物。不幸的是，病毒对这些药物表现出耐药性。这项研究的意义在于阐明没有一种药物能够以相同的效率治疗不同的基因型。因此，应根据 HCV 基因型开具治疗方案。
