{"doi":"10.1101/2023.02.10.528014","title":"Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p","abstract":"Abstract The stem loop 2 motif (s2m), a highly conserved 41-nucleotide hairpin structure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, serves as an attractive therapeutic target that may have important roles in the virus life cycle or interactions with the host. However, the conserved s2m in Delta SARS-CoV-2, a previously dominant variant characterized by high infectivity and disease severity, has received relatively less attention than that of the original SARS-CoV-2 virus. The focus of this work is to identify and define the s2m changes between Delta and SARS-CoV-2 and subsequent impact of those changes upon the s2m dimerization and interactions with the host microRNA miR-1307-3p. Bioinformatics analysis of the GISAID database targeting the s2m element reveals a greater than 99% correlation of a single nucleotide mutation at the 15 th position (G15U) in Delta SARS-CoV-2. Based on 1 H NMR assignments comparing the imino proton resonance region of s2m and the G15U at 19°C, we find that the U15-A29 base pair closes resulting in a stabilization of the upper stem without overall secondary structure deviation. Increased stability of the upper stem did not affect the chaperone activity of the viral N protein, as it was still able to convert the kissing dimers formed by s2m G15U into a stable duplex conformation, consistent with the s2m reference. However, we find that the s2m G15U mutation drastically reduces the binding affinity of the host miR-1307-3p. These findings demonstrate that the observed G15U mutation alters the secondary structure of s2m with subsequent impact on viral binding of host miR-1307-3p, with potential consequences on the immune response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398453,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1129439,"name":"Caleb J. Frye","orcid":"0000-0003-1301-2695","position":1,"is_corresponding":false},{"id":1129440,"name":"Joseph A. Makowski","orcid":"0000-0002-2597-8211","position":2,"is_corresponding":false},{"id":1129441,"name":"Adam H. Kensinger","orcid":"0000-0002-1931-9703","position":3,"is_corresponding":false},{"id":1129442,"name":"Morgan Shine","orcid":"0000-0002-8307-4210","position":4,"is_corresponding":false},{"id":1129799,"name":"Ella J. Milback","orcid":null,"position":5,"is_corresponding":false},{"id":598725,"name":"Patrick E. Lackey","orcid":"0000-0003-2528-1147","position":6,"is_corresponding":false},{"id":56680,"name":"Jeffrey D. Evanseck","orcid":"0000-0003-2616-7354","position":7,"is_corresponding":false},{"id":308437,"name":"Mihaela‐Rita Mihailescu","orcid":"0000-0002-1162-7699","position":8,"is_corresponding":false},{"id":1129438,"name":"Caylee L. Cunningham","orcid":"0000-0003-2716-4892","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":"36798421","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":[]}