{"doi":"10.1111/jcmm.13467","title":"Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein","abstract":"<jats:title>Abstract</jats:title><jats:p>Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (<jats:styled-content style=\"fixed-case\">NP</jats:styled-content>) is conserved among all influenza A viruses (<jats:styled-content style=\"fixed-case\">IAV</jats:styled-content>s) and has no cellular equivalent. Therefore, <jats:styled-content style=\"fixed-case\">NP</jats:styled-content> is an ideal target for the development of new <jats:styled-content style=\"fixed-case\">IAV</jats:styled-content> inhibitors. In this study, we identified a novel anti‐influenza compound, <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains <jats:italic>in vitro</jats:italic>, with an <jats:styled-content style=\"fixed-case\">IC</jats:styled-content><jats:sub>50</jats:sub> ranging from 0.41–1.14 μM. Furthermore, <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 inhibited the polymerase activity and specifically impaired the nuclear export of <jats:styled-content style=\"fixed-case\">NP</jats:styled-content>. Further investigation indicated that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 binds to the nuclear export signal 3 (<jats:styled-content style=\"fixed-case\">NES</jats:styled-content>3) domain and the dimer interface of the <jats:styled-content style=\"fixed-case\">NP</jats:styled-content> pocket. <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 also protected mice that were challenged with lethal doses of A/<jats:styled-content style=\"fixed-case\">PR</jats:styled-content>/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against <jats:styled-content style=\"fixed-case\">IAV</jats:styled-content>s in the future.</jats:p>","journal":"Journal of Cellular and Molecular Medicine","year":2018,"id":591520,"datarank":0.8049048052448528,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.3799228036364203,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.3799228036364203,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":13,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1513424,"name":"Jingliang Chen","orcid":null,"position":1,"is_corresponding":false},{"id":246691,"name":"Junsong Zhang","orcid":"0000-0002-7715-5006","position":2,"is_corresponding":false},{"id":1513426,"name":"Likai Tan","orcid":null,"position":3,"is_corresponding":false},{"id":1513427,"name":"Gui Lu","orcid":null,"position":4,"is_corresponding":false},{"id":1513428,"name":"Yongjie Luo","orcid":null,"position":5,"is_corresponding":false},{"id":1513429,"name":"Ting Pan","orcid":null,"position":6,"is_corresponding":false},{"id":1513430,"name":"Juanran Liang","orcid":null,"position":7,"is_corresponding":false},{"id":725838,"name":"Qianwen Li","orcid":"0000-0002-5553-227X","position":8,"is_corresponding":false},{"id":333379,"name":"Baohong Luo","orcid":"0009-0001-1514-2760","position":9,"is_corresponding":false},{"id":333387,"name":"Hui Zhang","orcid":"0000-0003-3620-610X","position":10,"is_corresponding":false},{"id":1513431,"name":"Gen Lu","orcid":null,"position":11,"is_corresponding":false},{"id":708677,"name":"Feng Huang","orcid":"0000-0001-6544-1999","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein","abstract":"<jats:title>Abstract</jats:title><jats:p>Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (<jats:styled-content style=\"fixed-case\">NP</jats:styled-content>) is conserved among all influenza A viruses (<jats:styled-content style=\"fixed-case\">IAV</jats:styled-content>s) and has no cellular equivalent. Therefore, <jats:styled-content style=\"fixed-case\">NP</jats:styled-content> is an ideal target for the development of new <jats:styled-content style=\"fixed-case\">IAV</jats:styled-content> inhibitors. In this study, we identified a novel anti‐influenza compound, <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains <jats:italic>in vitro</jats:italic>, with an <jats:styled-content style=\"fixed-case\">IC</jats:styled-content><jats:sub>50</jats:sub> ranging from 0.41–1.14 μM. Furthermore, <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 inhibited the polymerase activity and specifically impaired the nuclear export of <jats:styled-content style=\"fixed-case\">NP</jats:styled-content>. Further investigation indicated that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 binds to the nuclear export signal 3 (<jats:styled-content style=\"fixed-case\">NES</jats:styled-content>3) domain and the dimer interface of the <jats:styled-content style=\"fixed-case\">NP</jats:styled-content> pocket. <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 also protected mice that were challenged with lethal doses of A/<jats:styled-content style=\"fixed-case\">PR</jats:styled-content>/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that <jats:styled-content style=\"fixed-case\">ZBMD</jats:styled-content>‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against <jats:styled-content style=\"fixed-case\">IAV</jats:styled-content>s in the future.</jats:p>","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29193684","pmcid":"PMC5824420","openalex_id":"https://openalex.org/W2775828177","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81561128007","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81590765","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81601759","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81701990","title":null}],"total_grants":4,"fwci":0.491,"citation_percentile":0.67648395,"influential_citations":0,"citation_trend":[{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.13467","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.13467","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjcmm.13467","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13467","host_type":"publisher"},{"url":"https://doi.org/10.1111/jcmm.13467","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29193684","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5824420","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5824420","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5824420?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Influenza Virus Research Studies","interferon and immune responses","Viral gastroenteritis research and epidemiology","Active Transport, Cell Nucleus","Animals","Antiviral Agents","Humans","Influenza A Virus, H1N1 Subtype","Influenza A Virus, H3N2 Subtype","Influenza A virus","Inhibitory Concentration 50","Male","Mice, Inbred BALB C","Nucleocapsid Proteins","Orthomyxoviridae Infections","RNA-Binding Proteins","Small Molecule Libraries","Viral Core Proteins","Virus Replication"],"mesh_terms":["Animals","Antiviral Agents","Humans","Male","Mice, Inbred BALB C","Orthomyxoviridae Infections","Influenza A virus","Viral Core Proteins","Virus Replication","RNA-Binding Proteins","Nucleocapsid Proteins","Inhibitory Concentration 50","Active Transport, Cell Nucleus","Influenza A Virus, H1N1 Subtype","Influenza A Virus, H3N2 Subtype","Small Molecule Libraries"],"keywords":["Nucleoprotein","Nuclear export signal","Virology","Identification (biology)","Virus","Biology","Influenza A virus","Computational biology","Cell nucleus","Genetics","Gene","Nuclear Export","Compound Zbmd-1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-25T17:15:30.057267Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}