title: Human consensus interferons: Bridging the natural and artificial cytokines with intrinsic disorder.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nawal Abd
authors.initials: NA
authors.lastname: El-Baky
authors.affiliation: 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. Electronic address: vuversky@health.usf.edu.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: 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. Electronic address: redwan1961@yahoo.com.
authors.forename: Elrashdy M
authors.initials: EM
authors.lastname: Redwan
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry* / Q000627:therapeutic use; D007372:Interferons / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D064267:Intrinsically Disordered Proteins; D011994:Recombinant Proteins; C050739:interferon alfacon-1; D007372:Interferons
keywords: Artificial protein; Consensus interferon; Hepatitis C virus; Interferon; Protein intrinsic disorder