{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:18:24Z","timestamp":1784647104126,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rabies, a viral encephalitis caused by rabies virus (RABV), is 100% fatal upon the onset of symptoms. Effective post-exposure prophylaxis (PEP) measures are available, but they are often difficult to access in low-income countries. WHO estimates about 59,000 deaths due to rabies globally, and the majority are contributed by developing countries. Hence, developing drugs for the treatment of post-symptomatic rabies is an urgent and unmet demand. It is worth noting that previous efforts regarding antiviral strategies, such as small-interfering RNA, antibodies and small-molecule inhibitors, against the rabies virus have failed to show efficacy in pre-clinical studies, especially when the virus has reached the central nervous system (CNS). Therefore, drug repurposing seems to be an alternative tool for the development of new anti-rabies drugs. We validated and used a high-throughput, FITC-conjugated antibody-based flow cytometry assay to expedite the identification of repurposable new drug candidates against the RABV. The assay was validated using ribavirin and salinomycin as reference compounds, which showed EC50 values of 10.08 \u00b5M and 0.07 \u00b5M, respectively. We screened a SelleckChem library comprising 3035 FDA-approved compounds against RABV (CVS-11) at 10 \u00b5M concentration. Five compounds (clofazimine, tiamulin, difloxacin, harringtonine and homoharringtonine) were active against RABV, with greater than 90% inhibition. Homoharringtonine (HHT) identified in the present study is active against laboratory-adapted RABV (CVS-11) and clinical isolates of RABV, with an average EC50 of 0.3 \u00b5M in both BHK-21 and Neuro-2a cell lines and exhibits post-entry inhibition.<\/jats:p>","DOI":"10.3390\/v17070945","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:47:26Z","timestamp":1751600846000},"page":"945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Homoharringtonine Inhibits CVS-11 and Clinical Isolates of Rabies Virus In Vitro: Identified via High-Throughput Screening of an FDA-Approved Drug Library"],"prefix":"10.3390","volume":"17","author":[{"given":"Kalenahalli Rajappa","family":"Harisha","sequence":"first","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Kailaje","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder Reddy","family":"Kondreddi","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Sekhar","family":"Gudla","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shraddha","family":"Singh","sequence":"additional","affiliation":[{"name":"Veterinary College, Karnataka Veterinary, Animal and Fisheries Sciences University (KVAFSU), Hebbal, Bengaluru 560024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharada","family":"Ramakrishnaiah","sequence":"additional","affiliation":[{"name":"Veterinary College, Karnataka Veterinary, Animal and Fisheries Sciences University (KVAFSU), Hebbal, Bengaluru 560024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikrishna","family":"Isloor","sequence":"additional","affiliation":[{"name":"Veterinary College, Karnataka Veterinary, Animal and Fisheries Sciences University (KVAFSU), Hebbal, Bengaluru 560024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shridhar","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-1340","authenticated-orcid":false,"given":"Radha Krishan","family":"Shandil","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-5138","authenticated-orcid":false,"given":"Gudepalya Renukaiah","family":"Rudramurthy","sequence":"additional","affiliation":[{"name":"Foundation for Neglected Disease Research (FNDR), Bengaluru 561203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S1473-3099(19)30311-1","article-title":"A 1-Week Intradermal Dose-Sparing Regimen for Rabies Post-Exposure Prophylaxis (RESIST-2): An Observational Cohort Study","volume":"19","author":"Cantaert","year":"2019","journal-title":"Lancet Infect. 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