{"id":"W4409019601","doi":"10.1021/acs.jmedchem.4c02468","title":"From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants","year":2025,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"SARS-CoV-2 and COVID-19 Research","field":"Medicine","cited_by":9,"is_retracted":false,"has_abstract":true,"ca_institutions":"Princess Margaret Cancer Centre; University of Toronto; University of British Columbia; Simon Fraser University; Université de Sherbrooke","funders":"Faculty of Medicine and Health, University of Sydney; University of British Columbia; Government of Canada; University of Toronto; Canadian Institutes of Health Research; Faculty of Medicine, University of British Columbia; Simon Fraser University; Natural Sciences and Engineering Research Council of Canada; Université de Sherbrooke","keywords":"Protease inhibitor (pharmacology); Chemistry; Protease; Host (biology); Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Enzyme inhibitor; Coronavirus disease 2019 (COVID-19); Virology; Computational biology; Biochemistry; Virus; Enzyme; Biology; Genetics; Viral load","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":[0.0001389498,0.0003043001,0.0002186232,0.0001290021,0.00009032887,0.0002364528,0.0002457448,0.0001824016,0.0009830592],"category_scores_gemma":[0.00009587714,0.000104599,0.0001608218,0.000159377,0.0001270319,0.0001792434,0.0001832544,0.0003413899,0.0002585068],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002865113,"about_ca_system_score_gemma":0.0003122066,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001236156,"about_ca_topic_score_gemma":0.00386261,"domain_scores_codex":[0.9999282,0.00001049858,0.000008740573,0.00001217819,0.00002244942,0.00001796981],"domain_scores_gemma":[0.9999741,0.000003125924,0.000007358147,0.000001855698,0.000003403803,0.000010093],"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":[0.0006180061,0.0003382711,0.0007928928,0.0001175836,0.00002634581,0.0001976233,0.00003865668,0.002019062,0.9819129,0.000390837,0.0002580953,0.01328974],"study_design_scores_gemma":[0.0004638327,0.008674582,0.006915215,0.00003632821,0.00008794752,0.001253947,0.00007352924,0.006353675,0.9627548,0.0001708257,0.01317764,0.00003777994],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9926767,0.001546766,0.002278143,0.00007881739,0.00001743108,0.00008946294,0.0003230425,0.00005661837,0.002933135],"genre_scores_gemma":[0.9923265,0.001152852,0.004220362,0.0001242457,0.000004583803,0.00002918027,0.0004989989,0.00001393685,0.001629432],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001236156,"threshold_uncertainty_score":0.003288686,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02279612375630313,"score_gpt":0.3342752987134425,"score_spread":0.3114791749571393,"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."}}