{"doi":"10.1101/2020.06.09.134460","title":"A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein","abstract":"Abstract The function of the SARS-CoV-2 accessory protein p6, encoded by ORF6, is not fully known. Based upon its similarity to p6 from SARS-CoV, it may play a similar role, namely as an antagonist of type I interferon (IFN) signaling. Here we report the sequencing of a SARS-CoV-2 strain passaged six times after original isolation from a clinical patient in Hong Kong. The genome sequence shows a 27 nt in-frame deletion (Δ27,264-27,290) within ORF6, predicted to result in a 9 aa deletion ( ΔFKVSIWNLD ) from the central portion of p6. This deletion is predicted to result in a dramatic alteration in the three-dimensional structure of the resultant protein (p6 Δ22-30 ), possibly with significant functional implications. Analysis of the original clinical sample indicates that the deletion was not present, while sequencing of subsequent passages of the strain identifies the deletion as a majority variant. This suggests that the deletion originated ab initio during passaging and subsequently propagated into the majority, possibly due to the removal of selective pressure through the IFN-deficient Vero E6 cell line. The specific function of the SARS-CoV-2 p6 N-terminus, if any, has not yet been determined. However, this deletion is predicted to cause a shift from N-endo to N-ecto in the transmembrane localization of the SARS-CoV-2 p6 Δ22-30 N-terminus, possibly leading to the ablation of its native function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119294,"datarank":1.6160985209444627,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":1.1393904463922708,"self_endowment_contribution":0.47670807455219194,"citer_contribution":1.1393904463922708,"corpus_percentile":87.15092442175292,"corpus_rank":1662,"citation_count":23,"citer_count":23,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5658,"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":553992,"name":"Andrew M. Frank","orcid":"0000-0003-0411-7102","position":1,"is_corresponding":false},{"id":555001,"name":"Nikhita P. Puthuveetil","orcid":null,"position":2,"is_corresponding":false},{"id":555002,"name":"Beth Flores","orcid":null,"position":3,"is_corresponding":false},{"id":553993,"name":"M L Parker","orcid":"0000-0003-1803-3882","position":4,"is_corresponding":false},{"id":555003,"name":"Stephen Peter King","orcid":null,"position":5,"is_corresponding":false},{"id":7188,"name":"Malik Peiris","orcid":"0000-0001-8217-5995","position":6,"is_corresponding":false},{"id":106023,"name":"Daniel K. W. Chu","orcid":"0000-0002-9219-8979","position":7,"is_corresponding":false},{"id":555004,"name":"Briana Benton","orcid":null,"position":8,"is_corresponding":false},{"id":553994,"name":"Rebecca Bradford","orcid":"0000-0001-7998-3940","position":9,"is_corresponding":false},{"id":553995,"name":"Manzour Hernando Hazbón","orcid":"0000-0001-6967-815X","position":10,"is_corresponding":false},{"id":553996,"name":"Sujatha Rashid","orcid":"0000-0001-9967-8521","position":11,"is_corresponding":false},{"id":553991,"name":"Marco A. Riojas","orcid":"0000-0003-1119-1554","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","pmid":"32577643","pmcid":"PMC7302196","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":[]}