| Author | Silva, Allan Peres da | |
| Author | Antunes, Deborah | |
| Author | Torres, André Luiz Quintanilha | |
| Author | Caffarena, Ernesto Raul | |
| Author | Lampe, Elisabeth | |
| Access date | 2019-08-29T11:31:45Z | |
| Available date | 2019-08-29T11:31:45Z | |
| Document date | 2019 | |
| Citation | SILVA, Alan Peres da et al. E ects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease. Viruses, v. 11, n. 691, p. 1-17, 2019. | pt_BR |
| ISSN | 1999-4915 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/35175 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Vírus da Hepatite B | pt_BR |
| Subject in Portuguese | Polimorfismos | pt_BR |
| Subject in Portuguese | Simulação | pt_BR |
| Subject in Portuguese | Molecular dynamics | pt_BR |
| Subject in Portuguese | Análise de rede | pt_BR |
| Subject in Portuguese | Protease NS3 | pt_BR |
| Subject in Portuguese | Variante Q80K | pt_BR |
| Title | Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease | pt_BR |
| Type | Article | |
| DOI | 10.3390/v11080691 | |
| Abstract | Hepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulated. Based on HCV-1a clade I and II protein sequences, the structure of the HCV-1a Q80K mutant NS3-4A was obtained by comparative modeling. Its physicochemical properties were studied by molecular dynamics simulations and network analysis. Results demonstrate that, in the presence of the K80 variant, clade II protease polymorphisms A91 and S/G174 led to variations in hydrogen bond occupancies. Structural analyses revealed differences in (i) flexibility of the H57 catalytic residue on the NS3 protease and (ii) correlations between amino acids on the NS3 protease and the NS4A cofactor. The latter indicated possible destabilization of interactions, resulting in increased separation of these proteins. The present findings describe how the relationships between different HCV-1a NS3 protease amino acid residues could affect the appearance of viral variants and the existence of distinct genetic barriers to HCV-1a isolates. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Computacional e Sistemas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Departamento de Bioquímica. Laboratório de Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Hepatitis C virus | pt_BR |
| Subject | Q80K variant | pt_BR |
| Subject | Polymorphisms | pt_BR |
| Subject | NS3 protease | pt_BR |
| Subject | Simulation | pt_BR |
| Subject | Molecular dynamics | pt_BR |
| Subject | Network analysis | pt_BR |
| e-ISSN | 1999-4915 | |
