{"doi":"10.20944/preprints202104.0692.v1","title":"Host-Targeted Antivirals Inhibit RACK1-mediated IRES Activities in HIV-1 Infection","abstract":"Host ribosome-associated scaffold protein Receptor for Activated C Kinase 1 (RACK1) is utilized by a diverse group of human viruses for Internal Ribosomal Entry Sites (IRES) – mediated translation of viral mRNAs. We recently reported inhibition of herpes virus by small molecules targeting the RACK1 functional site. Here, we tested these molecules against HIV-1 and HCV, as HIV-1 contains two potential IRES sites and HCV translation occurs exclusively through IRES. Compounds significantly downregulated activities of HIV-1- and HCV-related dicistronic reporter constructs in transfected HEK293T cells. The compounds also strongly downregulated production of the HIV-1 capsid protein p24 in HIV-infected cells, as well as production of HIV-1 Gag precursor p55 and p55-derived proteins p24 and p17 in cells infected with the HIV-1 virus. Hepatitis C virus (HCV) IRES activities were also significantly inhibited by RACK1 inhibitor compounds. Since a number of human and plant pathogenic viruses are reported to use IRES, the RACK1 compounds can be established as broad host-targeted antivirals.","journal":"Preprints.org","year":2021,"id":220706,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":570107,"name":"Namita Kumari","orcid":"0000-0003-0893-9939","position":1,"is_corresponding":false},{"id":343439,"name":"Larisa Dubrovsky","orcid":null,"position":2,"is_corresponding":false},{"id":570582,"name":"Andrey Ivanov","orcid":null,"position":3,"is_corresponding":false},{"id":276950,"name":"Michael Bukrinsky","orcid":"0000-0002-8593-0770","position":4,"is_corresponding":false},{"id":24998,"name":"Sergeï Nekhai","orcid":"0000-0003-0744-7887","position":5,"is_corresponding":false},{"id":237104,"name":"Sivanesan Dakshanamurthy","orcid":"0000-0003-3681-4121","position":6,"is_corresponding":false},{"id":743782,"name":"Hemayet Ullah","orcid":"0000-0003-1748-3398","position":7,"is_corresponding":false},{"id":820392,"name":"Israa Abdullah Malli","orcid":"0000-0002-7361-5271","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:50.838581Z","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":[]}