{"doi":"10.1093/bib/bbab249","title":"Published anti-SARS-CoV-2 <i>in vitro</i> hits share common mechanisms of action that synergize with antivirals","abstract":"The global efforts in the past year have led to the discovery of nearly 200 drug repurposing candidates for COVID-19. Gaining more insights into their mechanisms of action could facilitate a better understanding of infection and the development of therapeutics. Leveraging large-scale drug-induced gene expression profiles, we found 36% of the active compounds regulate genes related to cholesterol homeostasis and microtubule cytoskeleton organization. Following bioinformatics analyses revealed that the expression of these genes is associated with COVID-19 patient severity and has predictive power on anti-SARS-CoV-2 efficacy in vitro. Monensin, a top new compound that regulates these genes, was further confirmed as an inhibitor of SARS-CoV-2 replication in Vero-E6 cells. Interestingly, drugs co-targeting cholesterol homeostasis and microtubule cytoskeleton organization processes more likely present a synergistic effect with antivirals. Therefore, potential therapeutics could be centered around combinations of targeting these processes and viral proteins.","journal":"Briefings in Bioinformatics","year":2021,"id":191086,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"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":417739,"name":"Shreya Paithankar","orcid":"0000-0002-9247-7847","position":1,"is_corresponding":false},{"id":756022,"name":"Ke Liu","orcid":"0000-0003-3190-1656","position":2,"is_corresponding":false},{"id":426800,"name":"Katie Uhl","orcid":"0000-0003-1889-9512","position":3,"is_corresponding":false},{"id":242007,"name":"Xiaopeng Li","orcid":"0000-0001-9655-9551","position":4,"is_corresponding":false},{"id":756023,"name":"Meehyun Ko","orcid":"0000-0003-4412-5545","position":5,"is_corresponding":false},{"id":556349,"name":"Seungtaek Kim","orcid":"0000-0003-3954-5908","position":6,"is_corresponding":false},{"id":756692,"name":"Jeremy S. Haskins","orcid":null,"position":7,"is_corresponding":false},{"id":11850,"name":"BIN CHEN","orcid":"0000-0001-8858-874X","position":8,"is_corresponding":false},{"id":272008,"name":"Jing Xing","orcid":"0000-0003-4726-8525","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:49:31.121780Z","pmid":"34245241","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":[]}