{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0001561408,0.0003384975,0.0003222773,0.0001210763,0.0001817261,0.0003786924,0.0003774038,0.0004589916,0.003203333],"category_scores_gemma":[0.0001490076,0.0001856228,0.0002548866,0.00009350458,0.0001984052,0.0003186487,0.0001697196,0.0008294928,0.0006271498],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0005147959,"about_ca_system_score_gemma":0.0004360912,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001425536,"about_ca_topic_score_gemma":0.002102095,"domain_scores_codex":[0.9999391,0.000008331214,0.000003737302,0.00001082425,0.00002209424,0.00001603135],"domain_scores_gemma":[0.9999572,0.000006297943,0.00001375082,0.000003173396,0.000007021764,0.00001261645],"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":[0.001220549,0.0002726234,0.003011575,0.0002552127,0.00007937827,0.002436978,0.0001610332,0.006022155,0.9703342,0.003336914,0.002518388,0.01035099],"study_design_scores_gemma":[0.0006090882,0.002534623,0.01433018,0.00007167076,0.0001974405,0.007477541,0.0003697049,0.04352776,0.8710566,0.002040921,0.05767989,0.0001045962],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9825775,0.003029362,0.006037519,0.0008718579,0.00009045333,0.00007403202,0.001198146,0.0002678334,0.005853288],"genre_scores_gemma":[0.9899297,0.000996266,0.004493618,0.0002359608,0.00001091984,0.00001403068,0.001364778,0.0000197161,0.002934919],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003203333,"threshold_uncertainty_score":0.0107162,"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."}}