{"id":"W4413309483","doi":"10.1039/d5md00356c","title":"Structural insights into the nirmatrelvir-resistant SARS-CoV-2 M<sup>pro</sup> L50F/E166A/L167F triple mutant-inhibitor-complex reveal strategies for next generation coronaviral inhibitor design","year":2025,"lang":"en","type":"article","venue":"RSC Medicinal Chemistry","topic":"SARS-CoV-2 and COVID-19 Research","field":"Medicine","cited_by":2,"is_retracted":false,"has_abstract":true,"ca_institutions":"University of Alberta","funders":"SLAC National Accelerator Laboratory; Biological and Environmental Research; Basic Energy Sciences; National Institute of General Medical Sciences; Institute of Infection and Immunity; Canadian Institutes of Health Research; Ministry of Advanced Education, Government of Alberta; Office of Science; National Institutes of Health; U.S. Department of Energy","keywords":"Mutant; Mutation; Viral replication; Chemistry; Protease; Protease inhibitor (pharmacology); Virology; Biology; Enzyme; Biochemistry; Virus; Viral load; Gene","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0007747128,0.0006870533,0.0009065294,0.0001768452,0.0007267211,0.0002795665,0.0006436074,0.0004848359,0.00004007306],"category_scores_gemma":[0.0005982251,0.0004873173,0.000339517,0.0006817441,0.0006482997,0.0003733351,0.0001770896,0.0009773223,0.00002212223],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0007121064,"about_ca_system_score_gemma":0.002278972,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003753502,"about_ca_topic_score_gemma":0.00005886416,"domain_scores_codex":[0.9954897,0.0001940512,0.001099868,0.0009982514,0.001282478,0.000935681],"domain_scores_gemma":[0.9976552,0.0004724831,0.0002610764,0.0009389675,0.0005385568,0.0001337481],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.002538316,0.0001098132,0.0001728616,0.001079986,0.0002002359,0.0001260673,0.001809822,0.00001388301,0.9706892,0.0003589352,0.01910121,0.003799669],"study_design_scores_gemma":[0.005131233,0.0005636004,0.0001226985,0.0004591918,0.0003069205,0.00009835271,0.004067303,0.02402746,0.9228543,0.001983573,0.03992306,0.0004622807],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9878657,0.003163851,0.002267217,0.00177592,0.0004470235,0.001876594,0.00003053298,0.0001900054,0.002383103],"genre_scores_gemma":[0.9848539,0.00002051911,0.0009401246,0.01016435,0.003032953,0.0003599035,0.0001775887,0.00007454235,0.0003761332],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.04783489,"threshold_uncertainty_score":0.9997578,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.09094352959369,"score_gpt":0.3513789867500972,"score_spread":0.2604354571564072,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}