Protective and Therapeutic Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City for Scientific Research and Technology Applications, New Borg EL Arab, 21934 Alexandria, Egypt.
Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia; Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia.
Cytokine Growth Factor Rev. 2015 Dec;26(6):637-45. doi: 10.1016/j.cytogfr.2015.07.012. Epub 2015 Jul 6.
The consensus interferons are artificially engineered proteins that combine most of the therapeutic features of natural human α-interferons and show high anti-cancer and anti-viral activities. Egyptian patients infected with hepatitis C virus (HCV) genotype 4 show lower responses to interferon (IFN) therapy than the distributed worldwide patients infected with the other HCV genotypes. Numerous studies have reported that patients with hepatitis C who have not responded to a previous standard IFN-alpha therapy or those who relapsed following treatment cessation may benefit from retreatment with consensus IFN-α (cIFN-α). IFNs-α are shown here to have functionally important disordered regions. Furthermore, a strong correlation is established between the peculiarities of disorder profiles of these proteins and their known structural features. Intrinsic disorder profiles of existing cIFNs-α possess remarkable similarity to the consensus disorder profile calculated as averaged disorder predispositions of all human IFNs-α. If the peculiarities of disorder distribution within the protein sequence are related to protein functionality, then comparison of the disorder profiles of artificial cIFNs (query profiles) with the averaged disorder predisposition profile of human IFNs-α (target profile) can be used in the design of novel cIFNs. The goal here would be to achieve a close similarity between the query and target profiles by manipulating the cIFN sequence.
共识干扰素是人工设计的蛋白质，它结合了天然人α干扰素的大部分治疗特性，并表现出高抗癌和抗病毒活性。感染丙型肝炎病毒（HCV）基因型 4 的埃及患者对干扰素（IFN）治疗的反应低于分布在世界各地的感染其他 HCV 基因型的患者。许多研究报告称，先前对标准 IFN-α 治疗无反应或在治疗停止后复发的丙型肝炎患者可能从共识 IFN-α（cIFN-α）的重新治疗中受益。IFN-α 在这里被证明具有功能上重要的无序区域。此外，还在这些蛋白质的无序特征与已知结构特征之间建立了很强的相关性。现有的 cIFN-α 的固有无序特征与作为所有人类 IFN-α 的平均无序倾向计算得出的共识无序特征非常相似。如果蛋白质序列内的无序分布的特点与蛋白质功能有关，那么将人工 cIFNs（查询特征）的无序特征与人类 IFN-α 的平均无序倾向特征（目标特征）进行比较可以用于新型 cIFNs 的设计。通过操纵 cIFN 序列，目标是在查询和目标特征之间实现紧密相似。
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