{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004378231,0.000153344,0.0003365049,0.00006617661,0.00002399643,0.000008776838,0.0002706742,0.0001634657,0.00006003597],"category_scores_gemma":[0.000222137,0.000111812,0.0001276583,0.0001661277,0.0001996499,0.000005688723,0.0001100344,0.0004083604,2.38608e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000042909,"about_ca_system_score_gemma":0.0005080493,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00002127149,"about_ca_topic_score_gemma":0.000004593007,"domain_scores_codex":[0.9986436,0.00005112306,0.0003728599,0.0002031522,0.0005065841,0.0002226991],"domain_scores_gemma":[0.9991559,0.00001512609,0.0002397368,0.0002175559,0.0002386327,0.0001330535],"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":[0.001957746,0.0003224624,0.001214661,0.0002620803,0.000102531,0.0001162747,0.00001757375,0.000004996705,0.9941353,0.000004884666,0.0008475475,0.001013909],"study_design_scores_gemma":[0.002323605,0.0002594588,0.001112269,0.0002987311,0.0000552712,0.0001208246,0.00009505881,0.000004723768,0.9909114,0.00001726056,0.00469991,0.0001014628],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9950127,0.001948481,0.000625289,0.0004815301,0.00006804844,0.0001306125,0.00001218629,0.000001727868,0.001719429],"genre_scores_gemma":[0.9978746,0.0001875342,0.0001923592,0.00006892611,0.0002857356,0.000005977971,0.000003363488,0.000009676885,0.001371804],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003852362,"threshold_uncertainty_score":0.455956,"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."}}