{"doi":"10.1101/2020.12.17.423211","title":"Identification of Celastrol as a novel HIV-1 Latency Reversal Agent by an Image-Based Screen","abstract":"Abstract Although current antiretroviral therapies (ART) are successful in controlling HIV-1 infection, a stable viral reservoir reactivates when ART is discontinued. Consequently, there is a major research effort to develop approaches to disrupt the latent viral reservoir and enhance the immune system’s ability to clear HIV-1. A number of small molecules, termed latency reversal agents (LRAs), have been identified which can reactivate latent HIV-1 in cell lines and patients’ cells ex vivo . However, clinical trials have suggested that combinations of LRAs will be required to efficiently reactivate HIV-1 in vivo , especially LRAs that act synergistically by functioning through distinct pathways. To identify novel LRAs, we used an image-based assay to screen a natural compound library for the ability to induce a low level of aggregation of resting primary CD4 + T cells from healthy donors. We identified celastrol as a novel LRA. Celastrol functions synergistically with other classes of LRA to reactivate latent HIV-1 in a Jurkat cell line, suggesting a novel mechanism in its LRA activity. Additionally, celastrol does not appear to activate resting CD4 + T cells at levels at which it can reactivate latent HIV-1. Celastrol appears to represent a novel class of LRAs and it therefore can serve as a lead compound for LRA development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131935,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559751,"name":"Pei-Wen Hu","orcid":null,"position":1,"is_corresponding":false},{"id":364432,"name":"Julien Dubrulle","orcid":"0000-0002-4186-7749","position":2,"is_corresponding":false},{"id":382939,"name":"Fabio Stossi","orcid":"0000-0001-6029-5478","position":3,"is_corresponding":false},{"id":586803,"name":"Bryan C. Nikolai","orcid":"0000-0002-9383-4404","position":4,"is_corresponding":false},{"id":382942,"name":"Michael A. Mancini","orcid":"0000-0002-4862-1944","position":5,"is_corresponding":false},{"id":586804,"name":"Andrew P. Rice","orcid":"0000-0002-1237-4769","position":6,"is_corresponding":false},{"id":586802,"name":"Hongbing Liu","orcid":"0000-0001-7718-3288","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:07.542484Z","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":[]}