Computational Study of HCV p7 Channel: Insight into a New Strategy for HCV Inhibitor Design

  • Beili Ying
  • Shichao Pang
  • Junchen Yang
  • Yang Zhong
  • Jingfang WangEmail author
Original Research Article


HCV p7 protein is a cation-selective ion channel, playing an essential role during the life cycle of HCV viruses. To understand the cation-selective mechanism, we constructed a hexameric model in lipid bilayers of HCV p7 protein for HCB JFH-1 strain, genotype 2a. In this structural model, His9 and Val6 were key factors for the HCV cation-selective ion channel. The histidine residues at position 9 in the hexameric model formed a first gate for HCV p7 channel, acting as a selectivity filter for cations. The valines mentioned above formed a second gate for HCV p7 channel, serving as a hydrophobic filter for the dehydrated cations. The binding pocket for the channel blockers, e.g., amantadine and rimantadine, was composed of residues 20–26 in H2 helix and 52–60 in H3 helix in i + 2 monomer. However, the molecular volumes for both amantadine and rimantadine were too small for the binding pocket of HCV p7 channel. Thus, designing a compound similar with rimantadine and having much larger volume would be an effective strategy for discovering inhibitors against HCV p7 channel. To achieve this point, we used rimantadine as a structural template to search ChEMBL database for the candidates employing favorable binding affinities to HCV p7 channel. As a result, six candidates were identified to have potential to be novel inhibitors against HCV p7 channel.


Hepatitis C virus P7 channel Structure-based drug design Molecular modeling 



This work was supported by the National Key Research and Development Program of China (no. 2016YFA0500600).


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Shanghai Center for Bioinformation TechnologyShanghaiChina
  3. 3.Department of Statistics, School of Mathematical SciencesShanghai Jiao Tong UniversityShanghaiChina
  4. 4.Department of Bioinformatics and Biostatistics, College of Life Science and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina
  5. 5.Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghaiChina

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