{"doi":"10.1101/2021.01.16.426970","title":"A <i>trans</i> -complementation system for SARS-CoV-2","abstract":"ABSTRACT The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research and countermeasure development. Here we report a trans -complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans -complementation system consists of two components: a genomic viral RNA containing a deletion of ORF3 and envelope gene, and a producer cell line expressing the two deleted genes. Trans- complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. The results suggest that the trans -complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":228496,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":286061,"name":"Yang Liu","orcid":"0009-0001-4290-9170","position":1,"is_corresponding":false},{"id":105302,"name":"Jianying Liu","orcid":"0000-0003-3855-8280","position":2,"is_corresponding":false},{"id":107150,"name":"Adam L. Bailey","orcid":"0000-0002-6560-9680","position":3,"is_corresponding":false},{"id":105318,"name":"Kenneth S. Plante","orcid":"0000-0002-7485-3167","position":4,"is_corresponding":false},{"id":105300,"name":"Jessica A. Plante","orcid":"0000-0002-4768-7458","position":5,"is_corresponding":false},{"id":105308,"name":"Jing Zou","orcid":"0000-0002-8098-7284","position":6,"is_corresponding":false},{"id":105303,"name":"Hongjie Xia","orcid":"0000-0002-2520-7038","position":7,"is_corresponding":false},{"id":108476,"name":"Nathen E. Bopp","orcid":null,"position":8,"is_corresponding":false},{"id":551105,"name":"Patricia Aguilar","orcid":null,"position":9,"is_corresponding":false},{"id":232720,"name":"Ping Ren","orcid":"0000-0002-4022-6667","position":10,"is_corresponding":false},{"id":105316,"name":"Vineet D. Menachery","orcid":"0000-0001-8803-7606","position":11,"is_corresponding":false},{"id":106529,"name":"Michael Diamond","orcid":"0000-0002-8791-3165","position":12,"is_corresponding":false},{"id":105319,"name":"Scott C. Weaver","orcid":"0000-0001-8016-8556","position":13,"is_corresponding":false},{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":14,"is_corresponding":false},{"id":38215,"name":"Pei‐Yong Shi","orcid":"0000-0001-5553-1616","position":15,"is_corresponding":false},{"id":105306,"name":"Xianwen Zhang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:50.414605Z","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":[]}