{"doi":"10.1021/acsomega.5c05856","title":"SARS-CoV-2 Papain-Like Protease Inhibitors Based on Naphthalen-1-ylethanamine and Halogenated Benzene Moieties","abstract":"High Resolution Image Download MS PowerPoint Slide Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative virus of COVID-19, remains a worldwide health threat. SARS-CoV-2 possesses two types of proteases: a main protease (M pro, 3C-like) and a papain-like protease (PL pro ). These proteases cleave two translated nonstructural proteins, pp1a and pp1ab, into viral functional proteins. In the present study, we developed new inhibitors targeting the PL pro of SARS-CoV-2 based on GRL-0048 ( 2 ) as a lead compound. Structure–activity relationship (SAR) researches on GRL-0048 ( 2 ) led to the finding of compound 9r, which showed significantly enhanced inhibitory activity against PL pro . This enhancement was accomplished by the introduction of a halogenated aromatic carbonyl moiety into the parent structure of GRL-0048 ( 2 ).","journal":"ACS Omega","year":2025,"id":534912,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"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":950458,"name":"Takuya Kobayakawa","orcid":"0000-0001-9786-2608","position":1,"is_corresponding":false},{"id":367621,"name":"Kohei Tsuji","orcid":"0000-0003-4773-8793","position":2,"is_corresponding":false},{"id":299087,"name":"Yuki Takamatsu","orcid":"0000-0001-7967-1576","position":3,"is_corresponding":false},{"id":295833,"name":"Hiroaki Mitsuya","orcid":"0000-0001-9274-3853","position":4,"is_corresponding":false},{"id":588041,"name":"Hirokazu Tamamura","orcid":"0000-0003-2788-2579","position":5,"is_corresponding":false},{"id":1117682,"name":"Kouki Shinohara","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"41114162","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":[]}