{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:51:04Z","timestamp":1760147464088,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, I.P. (FCT)","doi-asserted-by":"publisher","award":["PTDC\/QUI-OUT\/32572\/2017"],"award-info":[{"award-number":["PTDC\/QUI-OUT\/32572\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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\u2013protein interaction (PPI) sites of NS1 with PI3K and TRIM25, which suggests that these NS1 druggable pockets are promising new targets for antiviral development.<\/jats:p>","DOI":"10.3390\/ijms24032977","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"2977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling New Druggable Pockets in Influenza Non-Structural Protein 1: NS1\u2013Host Interactions as Antiviral Targets for Flu"],"prefix":"10.3390","volume":"24","author":[{"given":"Andreia E. S.","family":"Cunha","sequence":"first","affiliation":[{"name":"Coimbra Chemistry Center\u2014Institute of Molecular Sciences (CQC-IMS), Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Rui J. S.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Center\u2014Institute of Molecular Sciences (CQC-IMS), Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"given":"Carlos J. V.","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Center\u2014Institute of Molecular Sciences (CQC-IMS), Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"BSIM Therapeutics, Instituto Pedro Nunes, 3030-199 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-2557","authenticated-orcid":false,"given":"Rui M. M.","family":"Brito","sequence":"additional","affiliation":[{"name":"Coimbra Chemistry Center\u2014Institute of Molecular Sciences (CQC-IMS), Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"BSIM Therapeutics, Instituto Pedro Nunes, 3030-199 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of Global Seasonal Influenza-Associated Respiratory Mortality: A Modelling Study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"(2019). World Health Organization Global Influenza Strategy 2019\u20132030, Licence: CC BY-NC-SA 3.0 IGO. 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