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To date, neither therapeutics nor prophylactic approaches have been approved for MARV disease. The MARV matrix protein VP40 (mVP40) plays central roles in virus assembly and budding. mVP40 also inhibits interferon signaling by inhibiting the function of Janus kinase 1. This suppression of host antiviral defenses likely contributes to MARV virulence and therefore is a potential therapeutic target. We developed and optimized a cell-based high-throughput screening (HTS) assay in 384-well format to measure mVP40 interferon (IFN) antagonist function such that inhibitors could be identified. We performed a pilot screen of 1280 bioactive compounds and identified 3 hits, azaguanine-8, tosufloxacin hydrochloride, and linezolid, with Z scores &amp;gt; 3 and no significant cytotoxicity. Of these, azaguanine-8 inhibited MARV growth at noncytotoxic concentrations. These data demonstrate the suitability of the HTS mVP40 assay for drug discovery and suggest potential directions for anti-MARV therapeutic development.<\/jats:p>","DOI":"10.1021\/acsinfecdis.0c00512","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T15:42:09Z","timestamp":1598974929000},"page":"2783-2799","source":"Crossref","is-referenced-by-count":8,"title":["High-Throughput Screening Assay to Identify Small\nMolecule Inhibitors of Marburg Virus VP40 Protein"],"prefix":"10.1021","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7280-5292","authenticated-orcid":true,"given":"Priya","family":"Luthra","sequence":"first","affiliation":[{"name":"Trudeau Institute , , ,","place":["Saranac Lake, New York, United States, 12983-2100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Anantpadma","sequence":"additional","affiliation":[{"name":"WuXi App Tec , , ,","place":["Philadelphia, Pennsylvania, United States, 19112"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampriti","family":"De","sequence":"additional","affiliation":[{"name":"Georgia State University , , , ,","place":["Atlanta, Georgia, United States, 30302-3965"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Sourimant","sequence":"additional","affiliation":[{"name":"Georgia State University , , , ,","place":["Atlanta, Georgia, United States, 30302-3965"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Davey","sequence":"additional","affiliation":[{"name":"Boston University , , , ,","place":["Boston, Massachusetts, United States, 02118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K.","family":"Plemper","sequence":"additional","affiliation":[{"name":"Georgia State University , , , ,","place":["Atlanta, Georgia, United States, 30302-3965"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-425X","authenticated-orcid":true,"given":"Christopher F.","family":"Basler","sequence":"additional","affiliation":[{"name":"Georgia State University , , , ,","place":["Atlanta, Georgia, United States, 30302-3965"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"issue":"S12","key":"2026081722113853600_cit1","doi-asserted-by":"publisher","first-page":"S110","DOI":"10.1038\/nm1142","article-title":"Exotic emerging\nviral diseases: progress and challenges","volume":"10","author":"Geisbert","year":"2004","journal-title":"Nat.\nMed."},{"issue":"3","key":"2026081722113853600_cit2","doi-asserted-by":"publisher","first-page":"657","DOI":"10.7326\/0003-4819-71-3-657","article-title":"Green monkey disease (\u201d\u201cMarburg virus\u201d\u201c\u201d\ndisease): a new zoonosis","volume":"71","author":"Luby","year":"1969","journal-title":"Ann. 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