{"id":"W4410309472","doi":"10.1021/acs.jmedchem.5c00825","title":"Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity","year":2025,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Biochemical and Molecular Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":4,"is_retracted":false,"has_abstract":true,"ca_institutions":"Structural Genomics Consortium","funders":"Genentech; Janssen Biotech; Innovative Medicines Initiative; Center for Scientific Review; Ontario Genomics Institute; National Cancer Institute; European Federation of Pharmaceutical Industries and Associations; Structural Genomics Consortium; Merck KGaA; National Institutes of Health; Ontario Genomics; Genome Canada; Bayer; McGill University; Takeda Pharmaceuticals U.S.A.; Pfizer; Bristol-Myers Squibb; Boehringer Ingelheim","keywords":"Chemistry; In vivo; Enzyme inhibitor; Covalent bond; Metabolism; Protease inhibitor (pharmacology); Biochemistry; Enzyme; Covalent binding; Protease; Organic chemistry; Genetics; Virus; Biology","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":[0.0003199439,0.0004300417,0.0002298439,0.0001964262,0.0001191996,0.000248915,0.0002447207,0.0002865531,0.001635518],"category_scores_gemma":[0.0001908517,0.0001675794,0.0001834944,0.0001396662,0.0001458406,0.0002419152,0.00007202031,0.0004965265,0.0003366078],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002931936,"about_ca_system_score_gemma":0.0002482239,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0006207739,"about_ca_topic_score_gemma":0.0006611613,"domain_scores_codex":[0.9998804,0.00003514069,0.000006352701,0.00002226328,0.00002276207,0.00003305945],"domain_scores_gemma":[0.9998997,0.00002150683,0.00003524939,0.00001418657,0.00001089322,0.00001838222],"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":[0.001042955,0.0001796915,0.0001686803,0.00002698113,0.00001445255,0.00004180589,0.00001736239,0.0002184951,0.994733,0.00007001516,0.00009379506,0.003392825],"study_design_scores_gemma":[0.00004520958,0.003763883,0.001600341,0.00000280036,0.00002033872,0.0001926428,0.00000921757,0.001379125,0.9920764,0.00002012652,0.0008857195,0.000004266572],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9938242,0.001050812,0.002793798,0.00005840763,0.00001874302,0.00007296089,0.0003097934,0.0001067047,0.001764485],"genre_scores_gemma":[0.9932052,0.000798178,0.002059438,0.00003682545,0.00001291256,0.0000544651,0.000700886,0.0000314578,0.003100621],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001635518,"threshold_uncertainty_score":0.005471349,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.007548191438382664,"score_gpt":0.268763649301708,"score_spread":0.2612154578633253,"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."}}