{"doi":"10.1002/advs.202500798","title":"NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β‐TrCP1/FBXO5 Axis","abstract":"NSP7 (Non-Structural Protein 7) of SARS-CoV-2 is a crucial component for viral replication and transcription. In this study, it is revealed that the host E3 ubiquitin ligase FBXO5 suppresses viral replication by mediating NSP7 lysine-48-linked ubiquitination and subsequent proteasomal degradation. Interestingly, it is also determined that NSP7 expression impairs the host antiviral response by inhibiting the ISGylation of melanoma differentiation-associated protein 5 (MDA5), a key sensor for viral RNA. Through an unbiased esiRNA screen, it is identified that NSP7 ubiquitination is coregulated by β-TrCP1 and the kinase TAF1. Additionally, this study uncovers a small molecule FBXO5 stabilizer that disrupts the β-TrCP1-FBXO5 interaction, thereby markedly enhancing NSP7 degradation and effectively mitigating SARS-CoV-2 infection. Taken together, the findings reveal a novel mechanism for NSP7 regulation and suggest that small-molecule activators of the E3 ubiquitin ligase FBXO5 represent a promising new class of host-directed antiviral therapies.","journal":"Advanced Science","year":2025,"id":545007,"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":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344293,"name":"Travis Lear","orcid":"0000-0001-9156-0844","position":1,"is_corresponding":false},{"id":488055,"name":"Ferhan Tuncer","orcid":"0000-0003-4225-8627","position":2,"is_corresponding":false},{"id":722441,"name":"J. Villandre","orcid":null,"position":3,"is_corresponding":false},{"id":1109143,"name":"Áine N. Boudreau","orcid":"0000-0003-2943-7356","position":4,"is_corresponding":false},{"id":556358,"name":"Bo Lin","orcid":"0000-0002-2108-2696","position":5,"is_corresponding":false},{"id":315392,"name":"Irene Alfaras","orcid":"0000-0002-2073-9641","position":6,"is_corresponding":false},{"id":489336,"name":"Jason R. Kennerdell","orcid":null,"position":7,"is_corresponding":false},{"id":488056,"name":"Daniel P. Camarco","orcid":"0000-0001-7958-0658","position":8,"is_corresponding":false},{"id":496095,"name":"Mads Larsen","orcid":"0000-0001-5361-0898","position":9,"is_corresponding":false},{"id":1137492,"name":"Yun Hua","orcid":"0000-0002-0470-6671","position":10,"is_corresponding":false},{"id":488054,"name":"Yanwen Chen","orcid":"0000-0002-3467-2871","position":11,"is_corresponding":false},{"id":1435890,"name":"Meigin E. Chandler","orcid":null,"position":12,"is_corresponding":false},{"id":44869,"name":"Ricardo Pineda","orcid":"0000-0001-8768-4801","position":13,"is_corresponding":false},{"id":484913,"name":"Simon M. Barratt‐Boyes","orcid":"0000-0002-8869-4945","position":14,"is_corresponding":false},{"id":313758,"name":"John Evankovich","orcid":"0000-0003-2070-0883","position":15,"is_corresponding":false},{"id":271028,"name":"Toren Finkel","orcid":"0000-0002-0726-3546","position":16,"is_corresponding":false},{"id":488057,"name":"Yuan Liu","orcid":"0000-0001-5031-7514","position":17,"is_corresponding":false},{"id":344301,"name":"Bill B. Chen","orcid":"0000-0003-2695-5107","position":18,"is_corresponding":false},{"id":490480,"name":"Yao Tong","orcid":"0000-0001-6573-859X","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40577599","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":[]}