{"doi":"10.1021/acschembio.0c00975","title":"Inhibiting HTLV-1 Protease: A Viable Antiviral Target","abstract":"Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that can cause severe paralytic neurologic disease and immune disorders as well as cancer. An estimated 20 million people worldwide are infected with HTLV-1, with prevalence reaching 30% in some parts of the world. In stark contrast to HIV-1, no direct acting antivirals (DAAs) exist against HTLV-1. The aspartyl protease of HTLV-1 is a dimer similar to that of HIV-1 and processes the viral polyprotein to permit viral maturation. We report that the FDA-approved HIV-1 protease inhibitor darunavir (DRV) inhibits the enzyme with 0.8 μM potency and provides a scaffold for drug design against HTLV-1. Analogs of DRV that we designed and synthesized achieved submicromolar inhibition against HTLV-1 protease and inhibited Gag processing in viral maturation assays and in a chronically HTLV-1 infected cell line. Cocrystal structures of these inhibitors with HTLV-1 protease highlight opportunities for future inhibitor design. Our results show promise toward developing highly potent HTLV-1 protease inhibitors as therapeutic agents against HTLV-1 infections.","journal":"ACS Chemical Biology","year":2021,"id":173198,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524163,"name":"M. Henes","orcid":"0000-0001-8667-541X","position":1,"is_corresponding":false},{"id":266146,"name":"Nathaniel Talledge","orcid":"0000-0002-4603-0120","position":2,"is_corresponding":false},{"id":524161,"name":"L.N. Rusere","orcid":"0000-0001-9893-8694","position":3,"is_corresponding":false},{"id":524811,"name":"K. Kosovrasti","orcid":null,"position":4,"is_corresponding":false},{"id":524167,"name":"E.A. Nalivaika","orcid":"0000-0002-2654-1513","position":5,"is_corresponding":false},{"id":625369,"name":"Mohan Somasundaran","orcid":"0000-0001-7471-4530","position":6,"is_corresponding":false},{"id":524168,"name":"Akbar Ali","orcid":"0000-0003-3491-791X","position":7,"is_corresponding":false},{"id":409388,"name":"Louis M. Mansky","orcid":"0000-0003-2391-1061","position":8,"is_corresponding":false},{"id":249886,"name":"Neşe Kurt Yılmaz","orcid":"0000-0002-5036-676X","position":9,"is_corresponding":false},{"id":249895,"name":"Celia A. Schiffer","orcid":"0000-0003-2270-6613","position":10,"is_corresponding":false},{"id":524162,"name":"G.J. Lockbaum","orcid":"0000-0003-2720-6984","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:45.768135Z","pmid":"33619959","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":[]}