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https://hdl.handle.net/10316/114021
Título: | Unveiling New Druggable Pockets in Influenza Non-Structural Protein 1: NS1-Host Interactions as Antiviral Targets for Flu | Autor: | Cunha, Andreia E. S. Loureiro, Rui J. S. Simões, Carlos J. V. Brito, Rui M. M. |
Palavras-chave: | influenza; NS1; effector domain; molecular dynamics; druggability; protein–protein interactions; PI3K; TRIM25 | Data: | 3-Fev-2023 | Editora: | MDPI | Projeto: | PTDC/QUI-OUT/32572/2017 UIDB/00313/2020 CPCA/A0/7316/2020 PD/BD/143131/2018 UIDP/00013/2020 |
Título da revista, periódico, livro ou evento: | International Journal of Molecular Sciences | Volume: | 24 | Número: | 3 | Resumo: | Influenza viruses are responsible for significant morbidity and mortality worldwide in winter seasonal outbreaks and in flu pandemics. Influenza viruses have a high rate of evolution, requiring annual vaccine updates and severely diminishing the effectiveness of the available antivirals. Identifying novel viral targets and developing new effective antivirals is an urgent need. One of the most promising new targets for influenza antiviral therapy is non-structural protein 1 (NS1), a highly conserved protein exclusively expressed in virus-infected cells that mediates essential functions in virus replication and pathogenesis. Interaction of NS1 with the host proteins PI3K and TRIM25 is paramount for NS1's role in infection and pathogenesis by promoting viral replication through the inhibition of apoptosis and suppressing interferon production, respectively. We, therefore, conducted an analysis of the druggability of this viral protein by performing molecular dynamics simulations on full-length NS1 coupled with ligand pocket detection. We identified several druggable pockets that are partially conserved throughout most of the simulation time. Moreover, we found out that some of these druggable pockets co-localize with the most stable binding regions of the protein-protein interaction (PPI) sites of NS1 with PI3K and TRIM25, which suggests that these NS1 druggable pockets are promising new targets for antiviral development. | URI: | https://hdl.handle.net/10316/114021 | ISSN: | 1422-0067 | DOI: | 10.3390/ijms24032977 | Direitos: | openAccess |
Aparece nas coleções: | FCTUC Química - Artigos em Revistas Internacionais I&D CQC - Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Unveiling-New-Druggable-Pockets-in-Influenza-NonStructural-Protein-1-NS1Host-Interactions-as-Antiviral-Targets-for-FluInternational-Journal-of-Molecular-Sciences.pdf | 7.98 MB | Adobe PDF | Ver/Abrir |
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