{"doi":"10.1016/j.apsb.2026.03.008","title":"Identification and characterization of a non-nucleotide RdRp allosteric inhibitor with pan-coronavirus protection","abstract":null,"journal":"Acta Pharmaceutica Sinica B","year":2026,"id":637832,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1340137,"name":"Xiaomeng Yang","orcid":"0000-0002-4689-9301","position":1,"is_corresponding":false},{"id":1366577,"name":"Zhihao Zhao","orcid":"0009-0004-8973-8622","position":2,"is_corresponding":false},{"id":78586,"name":"Jian-Piao Cai","orcid":null,"position":3,"is_corresponding":false},{"id":749634,"name":"Liang Wei","orcid":"0000-0001-5276-0691","position":4,"is_corresponding":false},{"id":623070,"name":"Kaiming Tang","orcid":"0000-0001-7310-6744","position":5,"is_corresponding":false},{"id":868532,"name":"Wan-Mui Chan","orcid":"0000-0002-6137-8096","position":6,"is_corresponding":false},{"id":1656341,"name":"Allen Wing-Ho Chu","orcid":null,"position":7,"is_corresponding":false},{"id":1656342,"name":"Yixin Huang","orcid":"0009-0000-5791-4397","position":8,"is_corresponding":false},{"id":1656343,"name":"Tong-Yun Wang","orcid":null,"position":9,"is_corresponding":false},{"id":1244261,"name":"Yubin Xie","orcid":"0000-0002-3427-7986","position":10,"is_corresponding":false},{"id":791144,"name":"Yulan Liu","orcid":"0000-0001-5026-7828","position":11,"is_corresponding":false},{"id":623064,"name":"Zi‐Wei Ye","orcid":"0000-0002-6446-4299","position":12,"is_corresponding":false},{"id":245739,"name":"Tao Ni","orcid":"0000-0001-7268-0306","position":13,"is_corresponding":false},{"id":78574,"name":"Hin Chu","orcid":"0000-0003-2855-9837","position":14,"is_corresponding":false},{"id":78570,"name":"Jasper Fuk-Woo Chan","orcid":null,"position":15,"is_corresponding":false},{"id":78573,"name":"Kelvin Kai-Wang To","orcid":null,"position":16,"is_corresponding":false},{"id":72001,"name":"Kwok-Yung Yuen","orcid":"0000-0001-8700-4570","position":17,"is_corresponding":false},{"id":1656346,"name":"Ying-Chih Chiang","orcid":null,"position":18,"is_corresponding":false},{"id":78571,"name":"Shuofeng Yuan","orcid":"0000-0001-7996-1119","position":19,"is_corresponding":false},{"id":192970,"name":"Qian Guo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification and characterization of a non-nucleotide RdRp allosteric inhibitor with pan-coronavirus protection","abstract":"The viral RNA-dependent RNA polymerase (RdRp) is a conserved and compelling target for pan-coronavirus antiviral development. To date, all US Food and Drug Administration (FDA)-approved RdRp inhibitors are nucleotide inhibitors (NIs), which are prone to drug resistance and show limited clinical efficacy. Developing alternative non-nucleotide inhibitors (NNIs) with high target specificity, structural diversity, and metabolic stability could yield more effective antivirals. Here, we identify an allosteric RdRp NNI, BAY-850, via computational screening. BAY-850 exhibits potent, broad-spectrum antiviral activity against multiple SARS-CoV-2 variants and other human coronaviruses. Mechanistic studies show that BAY-850 binds directly to a previously unrecognized allosteric site on nsp12, thereby fine-tuning the catalytic motif F loop out-conformation the orthosteric site. Importantly, therapeutic administration of BAY-850 significantly reduces viral loads in the nasal turbinates and lungs of SARS-CoV-2-infected K18-hACE2 mice. These findings validate a novel allosteric site in RdRp and support BAY-850 as a start-point for broad-spectrum anti-coronavirus development. BAY-850 is a promising broad-spectrum anti-coronavirus candidate by targeting a novel allosteric site in RdRp","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W7134963351","authors":[],"funders":[{"funder_name":"Innovation and Technology Commission","grant_id":"GHP/231/22GD","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"C7002-23Y","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"32322087","title":null},{"funder_name":"Shenzhen Municipal Fundamental Research Program","grant_id":"JCYJ20250604180827037","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2407102445","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2023YFC3041600","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFA1300803","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC0866100","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2207101537","title":null}],"total_grants":9,"fwci":9.4584,"citation_percentile":0.96273218,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1016/j.apsb.2026.03.008","host_type":"journal"},{"url":"https://doi.org/10.1016/j.apsb.2026.03.008","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211383526001589?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2211383526001589?httpAccept=text/plain","host_type":"publisher"}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","COVID-19 Clinical Research Studies","Computational Drug Discovery Methods"],"mesh_terms":[],"keywords":["Allosteric regulation","RNA polymerase","Enzyme","Nucleotide","Drug discovery","Identification (biology)","Drug"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:36:40.459864Z","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":[]}