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Computational Study of HCV p7 Channel: Insight into a New Strategy for HCV Inhibitor Design.
Ying, Beili; Pang, Shichao; Yang, Junchen; Zhong, Yang; Wang, Jingfang.
Afiliação
  • Ying B; School of Life Sciences, Fudan University, Shanghai, 200433, China.
  • Pang S; Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, China.
  • Yang J; Department of Statistics, School of Mathematical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Zhong Y; Department of Bioinformatics and Biostatistics, College of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Wang J; School of Life Sciences, Fudan University, Shanghai, 200433, China.
Interdiscip Sci ; 11(2): 292-299, 2019 Jun.
Article em En | MEDLINE | ID: mdl-30194627
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Antivirais / Proteínas Virais / Desenho de Fármacos / Hepacivirus / Biologia Computacional Tipo de estudo: Prognostic_studies Idioma: En Revista: Interdiscip Sci Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Antivirais / Proteínas Virais / Desenho de Fármacos / Hepacivirus / Biologia Computacional Tipo de estudo: Prognostic_studies Idioma: En Revista: Interdiscip Sci Assunto da revista: BIOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China