{"doi":"10.1101/2024.01.02.573939","title":"Development of robust antiviral assays using relevant apical-out human airway organoids","abstract":"tools, standardization for drug discovery remains a challenge. This work introduces human airway organoids with reversed biopolarity (AORBs), cultured and analyzed in a high-throughput, single-organoid-per-well format, enabling milestones towards standardization. AORBs exhibit a spatio-temporally stable apical-out morphology, facilitating high-yield direct intact-organoid virus infection. Single-cell RNA sequencing and immunohistochemistry confirm the physiologically relevant recapitulation of differentiated human airway epithelia. The cellular tropism of five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains along with host response differences between Delta, Washington, and Omicron variants, as observed in transcriptomic profiles, also suggest clinical relevance. Dose-response analysis of three well-studied SARS-CoV-2 antiviral compounds (remdesivir, bemnifosbuvir, and nirmatrelvir) demonstrates that AORBs efficiently predict human efficacy, comparable to gold-standard air-liquid interface cultures, but with higher throughput (~10-fold) and fewer cells (~100-fold). This combination of throughput and relevance allows AORBs to robustly detect false negative results in efficacy, preventing irretrievable loss of promising lead compounds. While this work leverages the SARS-CoV-2 study as a proof-of-concept application, the standardization capacity of AORB holds broader implications in line with regulatory efforts to push alternatives to animal studies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484490,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":693450,"name":"Julia C. LeCher","orcid":"0000-0002-0056-176X","position":1,"is_corresponding":false},{"id":427842,"name":"Eric Parigoris","orcid":"0000-0002-7533-2558","position":2,"is_corresponding":false},{"id":1058663,"name":"Noriyuki Shinagawa","orcid":"0000-0001-9658-7667","position":3,"is_corresponding":false},{"id":406996,"name":"Jason Sentosa","orcid":"0000-0002-8721-8744","position":4,"is_corresponding":false},{"id":232935,"name":"Candela Manfredi","orcid":"0000-0001-7786-7444","position":5,"is_corresponding":false},{"id":900941,"name":"Shu Ling Goh","orcid":"0000-0001-8575-6103","position":6,"is_corresponding":false},{"id":929758,"name":"Ramyani De","orcid":"0000-0001-5534-0705","position":7,"is_corresponding":false},{"id":248189,"name":"Sijia Tao","orcid":null,"position":8,"is_corresponding":false},{"id":244969,"name":"Keivan Zandi","orcid":"0000-0001-9728-5038","position":9,"is_corresponding":false},{"id":314480,"name":"Franck Amblard","orcid":"0009-0002-6235-4050","position":10,"is_corresponding":false},{"id":232936,"name":"Eric J. Sorscher","orcid":"0000-0001-9341-3354","position":11,"is_corresponding":false},{"id":28520,"name":"Jason R. Spence","orcid":"0000-0001-7869-3992","position":12,"is_corresponding":false},{"id":393272,"name":"Rabindra Tirouvanziam","orcid":"0000-0003-3526-9985","position":13,"is_corresponding":false},{"id":228075,"name":"Raymond F. Schinazi","orcid":"0000-0002-6688-3614","position":14,"is_corresponding":false},{"id":282621,"name":"Shuichi Takayama","orcid":"0000-0002-4385-9080","position":15,"is_corresponding":false},{"id":282620,"name":"Ji‐Hoon Lee","orcid":"0000-0002-3542-3885","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:42.971417Z","pmid":"38260306","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":[]}