{"doi":"10.1093/ofid/ofab189","title":"In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2","abstract":"BACKGROUND: The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked researchers to propose multiple antiviral strategies to improve patients' outcomes. Studies provide evidence that cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro and decreases mortality rates of coronavirus disease 2019 (COVID-19) patients. CsA binds cyclophilins, which isomerize prolines, affecting viral protein activity. METHODS: We investigated the proline composition from various coronavirus proteomes to identify proteins that may critically rely on cyclophilin's peptidyl-proline isomerase activity and found that the nucleocapsid (N) protein significantly depends on cyclophilin A (CyPA). We modeled CyPA and N protein interactions to demonstrate the N protein as a potential indirect therapeutic target of CsA, which we propose may impede coronavirus replication by obstructing nucleocapsid folding. RESULTS: Finally, we analyzed the literature and protein-protein interactions, finding evidence that, by inhibiting CyPA, CsA may impact coagulation proteins and hemostasis. CONCLUSIONS: Despite CsA's promising antiviral characteristics, the interactions between cyclophilins and coagulation factors emphasize risk stratification for COVID patients with thrombosis dispositions.","journal":"Open Forum Infectious Diseases","year":2021,"id":202287,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"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":313409,"name":"David D. Holcomb","orcid":"0000-0002-4712-7952","position":1,"is_corresponding":false},{"id":313408,"name":"Jacob Kames","orcid":"0000-0002-1614-6915","position":2,"is_corresponding":false},{"id":308527,"name":"Anton A. Komar","orcid":"0000-0003-4188-0633","position":3,"is_corresponding":false},{"id":17114,"name":"Michael DiCuccio","orcid":"0000-0003-0585-2862","position":4,"is_corresponding":false},{"id":263286,"name":"Juan C. Ibla","orcid":"0000-0003-2096-5363","position":5,"is_corresponding":false},{"id":263287,"name":"Chava Kimchi‐Sarfaty","orcid":"0000-0002-9355-8585","position":6,"is_corresponding":false},{"id":561810,"name":"Kyle Laurie","orcid":"0000-0002-5596-6692","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:51:05.955461Z","pmid":"34109257","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":[]}