{"doi":"10.1016/j.bbrc.2019.05.064","title":"Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I","abstract":null,"journal":"Biochemical and Biophysical Research Communications","year":2019,"id":630768,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":961184,"name":"Yuan-Fang Wang","orcid":"0009-0004-8390-0561","position":1,"is_corresponding":false},{"id":961183,"name":"Andres Wong-Sam","orcid":"0000-0001-7997-6126","position":2,"is_corresponding":false},{"id":951061,"name":"Johnson Agniswamy","orcid":"0000-0002-3053-5677","position":3,"is_corresponding":false},{"id":233704,"name":"Arun K. Ghosh","orcid":"0000-0003-2472-1841","position":4,"is_corresponding":false},{"id":484835,"name":"Robert W. Harrison","orcid":"0000-0003-2449-1214","position":5,"is_corresponding":false},{"id":484834,"name":"Irene T. Weber","orcid":"0000-0003-4876-7393","position":6,"is_corresponding":false},{"id":759778,"name":"Shrikant Pawar","orcid":"0000-0002-6157-2462","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I","abstract":"HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PR<sub>Tri</sub>) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PR<sub>Tri</sub> mutant range from 17 to 40 nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PR<sub>Tri</sub> mutant in complex with inhibitor 1 at 1.5 Å resolution shows minor changes in interactions with inhibitor compared with the corresponding wild type PR complex. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. Hence, inhibition is influenced by small coordinated changes in hydrophobic interactions.","is_dataset_classified":null,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31092330","pmcid":"PMC6601333","openalex_id":"https://openalex.org/W2944795283","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"GM062920","title":null},{"funder_name":"National Institutes of Health","grant_id":"GM53386","title":null},{"funder_name":"U.S. Department of Energy","grant_id":"W-31-109-Eng-38","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM062920","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R37 GM053386","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM053386","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U01 AI150461","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"U01 GM062920","title":null}],"total_grants":8,"fwci":1.8974,"citation_percentile":0.85242391,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":7},{"year":2021,"count":1},{"year":2022,"count":5},{"year":2023,"count":2},{"year":2024,"count":5},{"year":2026,"count":2}],"oa_status":"green","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://www.osti.gov/servlets/purl/1531006","host_type":"repository"},{"url":"https://www.osti.gov/servlets/purl/1531006","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X19309349?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X19309349?httpAccept=text/plain","host_type":"publisher"},{"url":"https://www.osti.gov/biblio/1702259","host_type":"repository"},{"url":"https://doi.org/10.1016/j.bbrc.2019.05.064","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31092330","host_type":"repository"},{"url":"https://www.osti.gov/biblio/1531006","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6601333","host_type":"repository"}],"fields_of_study":["HIV/AIDS drug development and treatment","HIV Research and Treatment","Hepatitis C virus research","Amino Acid Substitution","Crystallography, X-Ray","Drug Resistance, Viral","HIV Infections","HIV Protease","HIV Protease Inhibitors","HIV-1","Humans","Models, Molecular","Point Mutation","Protein Conformation"],"mesh_terms":["Humans","Models, Molecular","Protein Conformation","HIV-1","HIV Infections","HIV Protease","HIV Protease Inhibitors","Point Mutation","Crystallography, X-Ray","Amino Acid Substitution","Drug Resistance, Viral"],"keywords":["Darunavir","Protease","HIV-1 protease","Protease inhibitor (pharmacology)","Mutant","Enzyme inhibitor","Wild type","Drug resistance","Chemistry","Drug","Mutation","Enzyme","Biology","Biochemistry","Stereochemistry","Human immunodeficiency virus (HIV)","Virology","Pharmacology","Genetics","Antiretroviral therapy","Viral load","X-ray crystallography","Antiviral Inhibitors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T22:07:27.325030Z","pmid":null,"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":[]}