{"doi":"10.1016/j.celrep.2023.113077","title":"SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility","abstract":"With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.","journal":"Cell Reports","year":2023,"id":321728,"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":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"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":107295,"name":"Eun-Ha Kim","orcid":null,"position":1,"is_corresponding":false},{"id":107301,"name":"Mark Anthony B. Casel","orcid":"0000-0002-8313-4076","position":2,"is_corresponding":false},{"id":107292,"name":"Young‐Il Kim","orcid":"0000-0002-0145-7382","position":3,"is_corresponding":false},{"id":987368,"name":"Rong Sun","orcid":"0000-0001-9719-3563","position":4,"is_corresponding":false},{"id":1035141,"name":"Mi-Jeong Kwak","orcid":null,"position":5,"is_corresponding":false},{"id":328255,"name":"Ji‐Seung Yoo","orcid":"0000-0002-3708-8240","position":6,"is_corresponding":false},{"id":1034428,"name":"Mina Yu","orcid":"0000-0003-4977-2741","position":7,"is_corresponding":false},{"id":651599,"name":"Kwang-Min Yu","orcid":"0000-0001-6692-6525","position":8,"is_corresponding":false},{"id":651602,"name":"Seung‐Gyu Jang","orcid":"0000-0001-9316-1652","position":9,"is_corresponding":false},{"id":651601,"name":"Rare Rollon","orcid":"0000-0002-8428-1713","position":10,"is_corresponding":false},{"id":987837,"name":"Jeong Ho Choi","orcid":null,"position":11,"is_corresponding":false},{"id":987369,"name":"Juryeon Gil","orcid":"0000-0002-9415-0688","position":12,"is_corresponding":false},{"id":987370,"name":"Kiyoung Eun","orcid":"0000-0001-9769-6136","position":13,"is_corresponding":false},{"id":987371,"name":"Hyunggee Kim","orcid":"0000-0002-5164-1663","position":14,"is_corresponding":false},{"id":517820,"name":"Armin Ensser","orcid":"0000-0001-8873-3863","position":15,"is_corresponding":false},{"id":987372,"name":"Jungwon Hwang","orcid":"0000-0002-4628-6177","position":16,"is_corresponding":false},{"id":107303,"name":"Min‐Suk Song","orcid":"0000-0001-6073-0783","position":17,"is_corresponding":false},{"id":835956,"name":"Myung Hee Kim","orcid":"0000-0003-2856-9066","position":18,"is_corresponding":false},{"id":107313,"name":"Jae U. Jung","orcid":"0000-0003-4559-8774","position":19,"is_corresponding":false},{"id":107314,"name":"Young Ki Choi","orcid":"0000-0002-0872-0147","position":20,"is_corresponding":false},{"id":651596,"name":"Se‐Mi Kim","orcid":"0000-0001-7932-1381","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:07:37.596550Z","pmid":"37676771","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":[]}