{"doi":"10.1128/aac.00646-15","title":"Microplate-Based Assay for Identifying Small Molecules That Bind a Specific Intersubunit Interface within the Assembled HIV-1 Capsid","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>Despite the availability of &gt;30 effective drugs for managing HIV-1 infection, no current therapy is curative, and long-term management is challenging owing to the emergence and spread of drug-resistant mutants. Identification of drugs against novel HIV-1 targets would expand the current treatment options and help to control resistance. The highly conserved HIV-1 capsid protein represents an attractive target because of its multiple roles in replication of the virus. However, the low antiviral potencies of the reported HIV-1 capsid–targeting inhibitors render them unattractive for therapeutic development. To facilitate the identification of more-potent HIV-1 capsid inhibitors, we developed a scintillation proximity assay to screen for small molecules that target a biologically active and specific intersubunit interface in the HIV-1 capsid. The assay, which is based on competitive displacement of a known capsid-binding small-molecule inhibitor, exhibited a signal-to-noise ratio of &gt;9 and a Z factor of &gt;0.8. In a pilot screen of a chemical library containing 2,400 druglike compounds, we obtained a hit rate of 1.8%. This assay has properties that are suitable for screening large compound libraries to identify novel HIV-1 capsid ligands with antiviral activity.</jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2015,"id":620402,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"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":334456,"name":"Jason P. Wong","orcid":"0000-0002-0710-3112","position":1,"is_corresponding":false},{"id":1169783,"name":"Bruce J. Melancon","orcid":"0000-0002-1958-0071","position":2,"is_corresponding":false},{"id":166788,"name":"Craig W. Lindsley","orcid":null,"position":3,"is_corresponding":false},{"id":307290,"name":"Christopher Aiken","orcid":"0000-0002-2476-4078","position":4,"is_corresponding":false},{"id":1601578,"name":"Upul D. Halambage","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Microplate-Based Assay for Identifying Small Molecules That Bind a Specific Intersubunit Interface within the Assembled HIV-1 Capsid","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>Despite the availability of &gt;30 effective drugs for managing HIV-1 infection, no current therapy is curative, and long-term management is challenging owing to the emergence and spread of drug-resistant mutants. Identification of drugs against novel HIV-1 targets would expand the current treatment options and help to control resistance. The highly conserved HIV-1 capsid protein represents an attractive target because of its multiple roles in replication of the virus. However, the low antiviral potencies of the reported HIV-1 capsid–targeting inhibitors render them unattractive for therapeutic development. To facilitate the identification of more-potent HIV-1 capsid inhibitors, we developed a scintillation proximity assay to screen for small molecules that target a biologically active and specific intersubunit interface in the HIV-1 capsid. The assay, which is based on competitive displacement of a known capsid-binding small-molecule inhibitor, exhibited a signal-to-noise ratio of &gt;9 and a Z factor of &gt;0.8. In a pilot screen of a chemical library containing 2,400 druglike compounds, we obtained a hit rate of 1.8%. This assay has properties that are suitable for screening large compound libraries to identify novel HIV-1 capsid ligands with antiviral activity.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26077250","pmcid":"PMC4538492","openalex_id":"https://openalex.org/W1883388481","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI114339","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"1U54MH084659-01","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI089401","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01-AI089401","title":null},{"funder_name":"NIMH NIH HHS","grant_id":"U54 MH084659","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01-AI114339","title":null}],"total_grants":6,"fwci":0.1502,"citation_percentile":0.4825496,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/59/9/5190.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/59/9/5190.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.00646-15","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.00646-15","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26077250","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4538492","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS drug development and treatment","Protein Structure and Dynamics","Anti-HIV Agents","Capsid","Capsid Proteins","Cell Line","HIV-1","Humans","Virus Replication"],"mesh_terms":["Capsid","Cell Line","Humans","Virus Replication","HIV-1","Anti-HIV Agents","Capsid Proteins"],"keywords":["Capsid","Small molecule","Drug discovery","Chemistry","Human immunodeficiency virus (HIV)","Virology","Computational biology","Virus","Biology","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T10:58:08.908530Z","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":[]}