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Structural Versatility of Hepatitis C Virus Proteins: Implications for the Design of Novel Anti-HCV Intervention Strategies

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Background: HCV-linked pathologies represent worldwide health threats. Over the years, an enormous number of independent studies have been devoted to the understanding of the molecular bases of HCV infection. A significant amount of these investigations has been focused on the structural characterization of the virus proteins with the aim of developing structure-based innovative therapeutic approaches. An analysis of the current Protein Data Bank content unravels that the structural biology of the virus has hitherto covered a large fraction of the HCV proteins (75%).

Objective: The present review recapitulates the state-of-the-art of structural characterizations of HCV individual proteins with a specific focus on their structural versatility/flexibility.

Results: This survey indicates there is accumulating evidence that structural flexibility is a common feature among HCV proteins. This versatility can be detected at different structural level i.e. occurrence of alternative oligomeric states and/or of local and global flexibility. Somewhat surprisingly, some disordered or highly flexible regions of HCV proteins, such as the core and the antigenic fragment 412-423 of E2, present highly conserved sequences among the virus genotypes. The overall versatility of HCV proteins plays an important role in host protein recognition, drug resistance mechanisms, and virus escape from the host immunogenic system. Of particular relevance is the emerging idea that HCV uses local structural flexibility as an alternative tool to sequence variability to evade the immune response of the host organism.

Conclusion: We believe that concepts emerged from this survey will be important for the development of anti-HCV vaccines that are eagerly needed.
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Keywords: Structural versatility; intrinsically disordered regions; structural biology; vaccine development; viral proteins

Document Type: Review Article

Publication date: November 1, 2017

This article was made available online on October 12, 2017 as a Fast Track article with title: "Structural Versatility of Hepatitis C Virus Proteins: Implications for the Design of Novel Anti-HCV Intervention Strategies".

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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