{"doi":"10.1194/jlr.r120000851","title":"Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity","abstract":"The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has resulted in the death of more than 328,000 persons worldwide in the first 5 months of 2020. Herculean efforts to rapidly design and produce vaccines and other antiviral interventions are ongoing. However, newly evolving viral mutations, the prospect of only temporary immunity, and a long path to regulatory approval pose significant challenges and call for a common, readily available, and inexpensive treatment. Strategic drug repurposing combined with rapid testing of established molecular targets could provide a pause in disease progression. SARS-CoV-2 shares extensive structural and functional conservation with SARS-CoV-1, including engagement of the same host cell receptor (angiotensin-converting enzyme 2) localized in cholesterol-rich microdomains. These lipid-enveloped viruses encounter the endosomal/lysosomal host compartment in a critical step of infection and maturation. Niemann-Pick type C (NP-C) disease is a rare monogenic neurodegenerative disease caused by deficient efflux of lipids from the late endosome/lysosome (LE/L). The NP-C disease-causing gene (NPC1) has been strongly associated with viral infection, both as a filovirus receptor (e.g., Ebola) and through LE/L lipid trafficking. This suggests that NPC1 inhibitors or NP-C disease mimetics could serve as anti-SARS-CoV-2 agents. Fortunately, there are such clinically approved molecules that elicit antiviral activity in preclinical studies, without causing NP-C disease. Inhibition of NPC1 may impair viral SARS-CoV-2 infectivity via several lipid-dependent mechanisms, which disturb the microenvironment optimum for viral infectivity. We suggest that known mechanistic information on NPC1 could be utilized to identify existing and future drugs to treat COVID-19.","journal":"Journal of Lipid Research","year":2020,"id":62584,"datarank":2.1626824320672844,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":1.5729085871586355,"self_endowment_contribution":0.5897738449086489,"citer_contribution":1.5729085871586355,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":50,"citers_with_citation_signal":45,"citers_with_endowment":45,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"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":332862,"name":"Tamayanthi Rajakumar","orcid":null,"position":1,"is_corresponding":false},{"id":331130,"name":"Natalie Hammond","orcid":"0000-0002-3340-2992","position":2,"is_corresponding":false},{"id":332863,"name":"Katsumi Higaki","orcid":null,"position":3,"is_corresponding":false},{"id":331131,"name":"Z. Márka","orcid":"0000-0003-1306-5260","position":4,"is_corresponding":false},{"id":44447,"name":"Szabolcs Márka","orcid":"0000-0002-3957-1324","position":5,"is_corresponding":false},{"id":331132,"name":"Andrew B. Munkacsi","orcid":"0000-0003-3033-395X","position":6,"is_corresponding":false},{"id":331129,"name":"Stephen L. Sturley","orcid":"0000-0001-6805-3270","position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:10:35.996198Z","pmid":"32457038","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":[]}