{"doi":"10.1073/pnas.2501389122","title":"Engineering a highly selective, hemoprotein-based scavenger as a carbon monoxide poisoning antidote with no hypertensive effect","abstract":"Carbon monoxide (CO) poisoning causes 50,000 to 100,000 emergency department visits and ~1,500 deaths in the United States annually. Current treatments are limited to supplemental and/or hyperbaric oxygen to accelerate CO elimination. Even with oxygen therapy, nearly half of CO poisoning survivors suffer long-term cardiac and neurocognitive deficits related to slow CO clearance, highlighting a need for point of care antidotal therapies. Given the natural interaction between CO and ferrous heme, we hypothesized that the hemoprotein RcoM, a transcriptional regulator of microbial CO metabolism, would make an ideal platform for CO-selective scavenging from endogenous hemoproteins. We engineered an RcoM truncate (RcoM-HBD-CCC) that exhibits high CO affinity ( K a,CO = 2.8 × 10 10 M −1 ), remarkable selectivity for CO over oxygen ( K a,O2 = 1.4 × 10 5 M −1 ; K a,CO / K a,O2 = 1.9 × 10 5 ), thermal stability (T m = 72 °C), and slow autoxidation rate ( k ox = 1.1 h −1 ). In a murine model of acute CO poisoning, infused RcoM-HBD-CCC accelerated CO clearance from hemoglobin in red blood cells (RBCs) and was rapidly excreted in urine. Moreover, infused RcoM-HBD-CCC elicited minimal hypertension in mice compared to infused globins (hemoglobin, myoglobin, and neuroglobin), attributed to a comparatively limited reactivity toward nitric oxide (NO) via dioxygenation [ k NOD (RcoM) = 6 to 8 × 10 6 M −1 s −1 vs k NOD (Hb) = 6 to 8 × 10 7 M −1 s −1 ]. These data suggest that RcoM-HBD-CCC is a safe, selective, and efficacious CO scavenger. By limiting hypertension through minimal NO scavenging, RcoM-HBD-CCC improves end-organ adverse effects compared with other hemoprotein-based therapeutics.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":539816,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414284,"name":"Anthony W. 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Baker","orcid":"0000-0002-3147-4925","position":11,"is_corresponding":false},{"id":1427321,"name":"Ajay Ram Srimath Kandada","orcid":"0000-0002-7420-1150","position":12,"is_corresponding":false},{"id":1427745,"name":"Angka Bulbul","orcid":null,"position":13,"is_corresponding":false},{"id":347800,"name":"Daniel B. Kim‐Shapiro","orcid":"0000-0003-4383-3101","position":14,"is_corresponding":false},{"id":414287,"name":"Jason J. Rose","orcid":"0000-0003-1347-9148","position":15,"is_corresponding":false},{"id":347796,"name":"Jesús Tejero","orcid":"0000-0003-3245-9978","position":16,"is_corresponding":false},{"id":24963,"name":"Mark T. Gladwin","orcid":"0000-0001-7267-9006","position":17,"is_corresponding":false},{"id":642204,"name":"Matthew R. Dent","orcid":"0000-0002-7704-4867","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:34.520788Z","pmid":"40763026","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}