Molecular modelling analysis of T219A mutant envelope protein revealed novel virulence enhancing factors in Dengue virus isolated from Kerala state, India.
Comput Methods Programs Biomed
; 195: 105481, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32497770
ABSTRACT
Dengue virus (DENV) is an emerging health threat and its envelope glycoprotein E, is involved in the anchoring and fusion mechanisms. Anchoring followed by conformational changes of E-protein are responsible for the fusion and entry of DENV into host. The variation in the conformation of the E-protein due to mutations, results in its altered binding with antibodies (Abs) and also its receptors. This leads to failure of neutralization of DENV and enhance the infection. In our earlier studies we have identified T219A mutation in the E-protein of DENV and the present study is focused on the impact of this mutation on the conformation of E-protein and also its binding variation with Abs and Fc-γ receptor. A comparative molecular modelling studies of wild type and T219A mutant E-proteins revealed that, the mutation induced several conformational variations in the E-protein and resulted in the variable binding orientation with altered affinities. Further, the mutation was also observed to enhance the fusion mechanism by Fc-γ receptors that mediate the efficient entry of DENV into host cell through altered membrane fusion mechanism. Such conformational variations of E-protein could be the responsible factors for enhanced virulence of DENV infections.
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Base de dados:
MEDLINE
Assunto principal:
Dengue
/
Vírus da Dengue
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article