{"doi":"10.1101/2021.12.18.473309","title":"The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness","abstract":"During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure. ONE-SENTENCE SUMMARY: Efficient Editing of SARS-CoV-2 genomic RNA by Host APOBEC deaminases and Its Potential Impacts on the Viral Replication and Emergence of New Strains in COVID-19 Pandemic.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213617,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"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":805694,"name":"Peter Calabrese","orcid":"0000-0002-7342-5013","position":1,"is_corresponding":false},{"id":805695,"name":"Shanshan Wang","orcid":"0009-0000-7215-6555","position":2,"is_corresponding":false},{"id":678826,"name":"Chao Qin","orcid":"0000-0003-0393-1751","position":3,"is_corresponding":false},{"id":678828,"name":"Youliang Rao","orcid":"0000-0002-8416-8104","position":4,"is_corresponding":false},{"id":180721,"name":"Pinghui Feng","orcid":null,"position":5,"is_corresponding":false},{"id":318117,"name":"Xiaojiang S. Chen","orcid":"0000-0001-9574-0551","position":6,"is_corresponding":false},{"id":805693,"name":"Kyumin Kim","orcid":"0000-0002-1880-7801","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:36.886828Z","pmid":"34981048","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":[]}