{"doi":"10.1073/pnas.2003056117","title":"A cocrystal structure of dengue capsid protein in complex of inhibitor","abstract":"Dengue virus (DENV) was designated as a top 10 public health threat by the World Health Organization in 2019. No clinically approved anti-DENV drug is currently available. Here we report the high-resolution cocrystal structure (1.5 Å) of the DENV-2 capsid protein in complex with an inhibitor that potently suppresses DENV-2 but not other DENV serotypes. The inhibitor induces a \"kissing\" interaction between two capsid dimers. The inhibitor-bound capsid tetramers are assembled inside virions, resulting in defective uncoating of nucleocapsid when infecting new cells. Resistant DENV-2 emerges through one mutation that abolishes hydrogen bonds in the capsid structure, leading to a loss of compound binding. Structure-based analysis has defined the amino acids responsible for the inhibitor's inefficacy against other DENV serotypes. The results have uncovered an antiviral mechanism through inhibitor-induced tetramerization of the viral capsid and provided essential structural and functional knowledge for rational design of panserotype DENV capsid inhibitors.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":97892,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8812,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":1,"is_corresponding":false},{"id":105308,"name":"Jing Zou","orcid":"0000-0002-8098-7284","position":2,"is_corresponding":false},{"id":139653,"name":"Christian G. Noble","orcid":null,"position":3,"is_corresponding":false},{"id":250363,"name":"William K. Russell","orcid":"0000-0003-1931-4555","position":4,"is_corresponding":false},{"id":421626,"name":"Luis Marcelo F. Holthauzen","orcid":"0000-0001-6130-1729","position":5,"is_corresponding":false},{"id":371054,"name":"Kyung H. Choi","orcid":"0000-0003-0865-1265","position":6,"is_corresponding":false},{"id":483492,"name":"Mark A. White","orcid":"0000-0003-1057-4203","position":7,"is_corresponding":false},{"id":38215,"name":"Pei‐Yong Shi","orcid":"0000-0001-5553-1616","position":8,"is_corresponding":false},{"id":105303,"name":"Hongjie Xia","orcid":"0000-0002-2520-7038","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32669438","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":[]}