{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:04:51Z","timestamp":1788314691679,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272200700016I, HHSN272201800013C"],"award-info":[{"award-number":["HHSN272200700016I, HHSN272201800013C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody-based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. Using this assay, we screened nearly 3000 small molecules and identified several molecules with the desired inhibitory properties. In secondary assays, one identified compound, sangivamycin, inhibited not only Ebola viral infectivity but also that of other viruses. This finding indicates that it is possible for this new VP40-based screening method to identify highly potent MCMs against Ebola virus and its relatives.<\/jats:p>","DOI":"10.3390\/v13010052","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T14:31:49Z","timestamp":1609425109000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-9721","authenticated-orcid":false,"given":"Ryan P.","family":"Bennett","sequence":"first","affiliation":[{"name":"OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3674-3282","authenticated-orcid":false,"given":"Courtney L.","family":"Finch","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0275-2148","authenticated-orcid":false,"given":"Elena N.","family":"Postnikova","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Stewart","sequence":"additional","affiliation":[{"name":"OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-0920","authenticated-orcid":false,"given":"Yingyun","family":"Cai","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9473-566X","authenticated-orcid":false,"given":"Shuiqing","family":"Yu","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janie","family":"Liang","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-4183","authenticated-orcid":false,"given":"Julie","family":"Dyall","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-3104","authenticated-orcid":false,"given":"Jason D.","family":"Salter","sequence":"additional","affiliation":[{"name":"OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6257-6791","authenticated-orcid":false,"given":"Harold C.","family":"Smith","sequence":"additional","affiliation":[{"name":"OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-6045","authenticated-orcid":false,"given":"Jens H.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"NIH\/NIAID\/DCR\/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","first-page":"449","article-title":"Filoviridae","volume":"Volume 1","author":"Howley","year":"2020","journal-title":"Fields Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1099\/jgv.0.001252","article-title":"ICTV Report Consortium, ICTV virus taxonomy profile: Filoviridae","volume":"100","author":"Kuhn","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41579-019-0187-4","article-title":"New filovirus disease classification and nomenclature","volume":"17","author":"Kuhn","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bullard, S.G. (2018). A Day-by-Day Chronicle of the 2013\u20132016 Ebola Outbreak, Springer.","DOI":"10.1007\/978-3-319-76565-5"},{"key":"ref_5","unstructured":"World Health Organization (2020, December 30). Ebola in the Democratic Republic of the Congo, North Kivu, Ituri 2018\u20132020. Available online: https:\/\/www.who.int\/emergencies\/diseases\/ebola\/drc-2019."},{"key":"ref_6","first-page":"1027","article-title":"Ebola, des premiers vaccins disponibles","volume":"36","author":"Martin","year":"2020","journal-title":"M\u00e9d. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1056\/NEJMoa1910993","article-title":"PALM Writing Group, A randomized, controlled trial of Ebola virus disease therapeutics","volume":"381","author":"Mulangu","year":"2019","journal-title":"N Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature17180","article-title":"Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys","volume":"531","author":"Warren","year":"2016","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schindell, B.G., Webb, A.L., and Kindrachuk, J. (2018). Persistence and sexual transmission of filoviruses. Viruses, 10.","DOI":"10.3390\/v10120683"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.celrep.2015.08.038","article-title":"Emergence of Ebola virus escape variants in infected nonhuman primates treated with the MB-003 antibody cocktail","volume":"12","author":"Kugelman","year":"2015","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e231","DOI":"10.1016\/S1473-3099(20)30282-6","article-title":"Recent successes in therapeutics for Ebola virus disease: No time for complacency","volume":"20","author":"Iversen","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41579-019-0233-2","article-title":"Therapeutic strategies to target the Ebola virus life cycle","volume":"17","author":"Hoenen","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S612","DOI":"10.1093\/infdis\/jiy285","article-title":"Development of clinical-stage human monoclonal antibodies that treat advanced Ebola virus disease in nonhuman primates","volume":"218","author":"Pascal","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S672","DOI":"10.1093\/infdis\/jiy304","article-title":"Identification of combinations of approved drugs with synergistic activity against Ebola virus in cell cultures","volume":"218","author":"Dyall","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1093\/cid\/ciw571","article-title":"Clinical and virological characteristics of Ebola virus disease patients treated with favipiravir (T-705)-Sierra Leone, 2014","volume":"63","author":"Bai","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sissoko, D., Laouenan, C., Folkesson, E., M\u2019Lebing, A.-B., Beavogui, A.H., Baize, S., Camara, A.-M., Maes, P., Shepherd, S., and Danel, C. (2016). JIKI Study Group, Experimental treatment with favipiravir for Ebola virus disease (the JIKI Trial): A historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002066"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/infdis\/jiz078","article-title":"Laboratory findings, compassionate use of favipiravir, and outcome in patients with Ebola virus disease, Guinea, 2015-a retrospective observational study","volume":"220","author":"Kerber","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2183\/pjab.93.027","article-title":"Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase","volume":"93","author":"Furuta","year":"2017","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nature13027","article-title":"Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430","volume":"508","author":"Warren","year":"2014","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.cell.2013.07.015","article-title":"Structural rearrangement of Ebola virus VP40 begets multiple functions in the virus life cycle","volume":"154","author":"Bornholdt","year":"2013","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1002\/pro.2541","article-title":"Conformational plasticity of the Ebola virus matrix protein","volume":"23","author":"Radzimanowski","year":"2014","journal-title":"Protein Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1093\/emboj\/19.16.4228","article-title":"Crystal structure of the matrix protein VP40 from Ebola virus","volume":"19","author":"Dessen","year":"2000","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2001.0860","article-title":"Vesicular release of Ebola virus matrix protein VP40","volume":"283","author":"Timmins","year":"2001","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6732","DOI":"10.1093\/emboj\/19.24.6732","article-title":"Membrane association induces a conformational change in the Ebola virus matrix protein","volume":"19","author":"Scianimanico","year":"2000","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1128\/JVI.00737-10","article-title":"Oligomerization of Ebola virus VP40 is essential for particle morphogenesis and regulation of viral transcription","volume":"84","author":"Hoenen","year":"2010","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.virol.2010.04.002","article-title":"Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription","volume":"403","author":"Hoenen","year":"2010","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1128\/JVI.79.3.1898-1905.2005","article-title":"VP40 octamers are essential for Ebola virus replication","volume":"79","author":"Hoenen","year":"2005","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1128\/JVI.01087-15","article-title":"Host cell plasma membrane phosphatidylserine regulates the assembly and budding of Ebola virus","volume":"89","author":"Johnson","year":"2015","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1074\/jbc.M112.443960","article-title":"The Ebola virus matrix protein penetrates into the plasma membrane: A key step in VP40 oligomerization and viral egress","volume":"288","author":"Soni","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-28077-7","article-title":"A cylindrical assembly model and dynamics of the Ebola virus VP40 structural matrix","volume":"8","author":"Pavadai","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0969-2126(03)00050-9","article-title":"The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties","volume":"11","author":"Dessen","year":"2003","journal-title":"Structure"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Silva, L.P., Vanzile, M., Bavari, S., Aman, J.M., and Schriemer, D.C. (2012). Assembly of Ebola virus matrix protein VP40 is regulated by latch-like properties of N and C terminal tails. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039978"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S291","DOI":"10.1086\/520595","article-title":"Mapping of a region of Ebola virus VP40 that is important in the production of virus-like particles","volume":"196","author":"Yamayoshi","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-981-10-8456-0_4","article-title":"Filovirus filament proteins","volume":"88","author":"Beniac","year":"2018","journal-title":"Subcell Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Noda, T., Ebihara, H., Muramoto, Y., Fujii, K., Takada, A., Sagara, H., Kim, J.H., Kida, H., Feldmann, H., and Kawaoka, Y. (2006). Assembly and budding of Ebolavirus. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020099"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cong, Y., Dyall, J., Hart, B.J., DeWald, L.E., Johnson, J.C., Postnikova, E., Zhou, H., Gross, R., Rojas, O., and Alexander, I. (2016). Evaluation of the activity of lamivudine and zidovudine against Ebola virus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166318"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cong, Y., McArthur, M.A., Cohen, M., Jahrling, P.B., Janosko, K.B., Josleyn, N., Kang, K., Zhang, T., and Holbrook, M.R. (2016). Characterization of yellow fever virus infection of human and non-human primate antigen presenting cells and their interaction with CD4+ T cells. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004709"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1006\/bbrc.1998.9646","article-title":"Development of a bicistronic vector driven by the human polypeptide chain elongation factor 1\u03b1 promoter for creation of stable mammalian cell lines that express very high levels of recombinant proteins","volume":"252","author":"Hobbs","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Postnikova, E., Cong, Y., DeWald, L.E., Dyall, J., Yu, S., Hart, B.J., Zhou, H., Gross, R., Logue, J., and Cai, Y. (2018). Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194880"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.virusres.2007.04.014","article-title":"In vivo imaging of cidofovir treatment of cowpox virus infection","volume":"128","author":"Goff","year":"2007","journal-title":"Virus Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ni762","article-title":"Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo","volume":"3","author":"Norbury","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1128\/jvi.49.3.857-864.1984","article-title":"General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes","volume":"49","author":"Mackett","year":"1984","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"190ra79","DOI":"10.1126\/scitranslmed.3005471","article-title":"FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection","volume":"5","author":"Johansen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nature18615","article-title":"Toremifene interacts with and destabilizes the Ebola virus glycoprotein","volume":"535","author":"Zhao","year":"2016","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3181\/00379727-151-39241","article-title":"Effect of cytosine, arabinoside, iododeoxyuridine, ethyldeoxyuridine, thiocyanatodeoxyuridine, and ribavirin on tail lesion formation in mice infected with vaccinia virus","volume":"151","author":"Luczak","year":"1976","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"34580","DOI":"10.1074\/jbc.M807029200","article-title":"Induction of protein kinase PKR-dependent activation of interferon regulatory factor 3 by vaccinia virus occurs through adapter IPS-1 signaling","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_47","first-page":"298","article-title":"Pathology of experimental Ebola-Zaire (Mayinga) virus infection transmitted to guinea-pigs by oral, conjunctival and tonsillar routes","volume":"4","author":"Vogel","year":"1997","journal-title":"Cell Vision"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1099\/0022-1317-72-3-549","article-title":"Antigenic relatedness between arenaviruses defined at the epitope level by monoclonal antibodies","volume":"72","author":"Ruo","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.antiviral.2016.11.001","article-title":"An analog of camptothecin inactive against topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation","volume":"136","author":"Bennett","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1128\/JVI.72.4.2855-2864.1998","article-title":"Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1","volume":"72","author":"Platt","year":"1998","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.virol.2013.03.013","article-title":"The L-VP35 and L-L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals","volume":"441","author":"Trunschke","year":"2013","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.antiviral.2011.06.003","article-title":"Minigenomes, transcription and replication competent virus-like particles and beyond: Reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses","volume":"91","author":"Hoenen","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_53","first-page":"1784","article-title":"Kinetic effects of sangivamycin in sarcoma 180 in vitro","volume":"41","author":"Ritch","year":"1981","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-53223-0","article-title":"Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death","volume":"9","author":"Bastea","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15271","DOI":"10.1074\/jbc.M701362200","article-title":"The nucleoside analog sangivamycin induces apoptotic cell death in breast carcinoma MCF7\/adriamycin-resistant cells via protein kinase C\u03b4 and JNK activation","volume":"282","author":"Lee","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbrc.2014.01.017","article-title":"Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells","volume":"444","author":"Wakao","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tchesnokov, E.P., Feng, J.Y., Porter, D.P., and G\u00f6tte, M. (2019). Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses, 11.","DOI":"10.3390\/v11040326"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3389\/fphar.2019.01222","article-title":"Isobologram analysis: A comprehensive review of methodology and current research","volume":"10","author":"Huang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/S0021-9258(19)77930-7","article-title":"Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C","volume":"263","author":"Loomis","year":"1988","journal-title":"J. Biol Chem"},{"key":"ref_60","first-page":"197","article-title":"Initial toxicity study of sangivamycin (NSC-65346)","volume":"51","author":"Cavins","year":"1967","journal-title":"Cancer Chemother Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102","DOI":"10.7164\/antibiotics.42.102","article-title":"A new biological role of sangivamycin; inhibition of protein kinases","volume":"42","author":"Osada","year":"1989","journal-title":"J. Antibiot."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2407-9-63","article-title":"ARC (NSC 188491) has identical activity to sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC","volume":"9","author":"Stockwin","year":"2009","journal-title":"BMC Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1021\/jm500089r","article-title":"Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target","volume":"57","author":"Lin","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/AAC.30.5.719","article-title":"Xylotubercidin against herpes simplex virus type 2 in mice","volume":"30","author":"Robins","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3109\/02713688709020100","article-title":"The antiherpesvirus activity and cytotoxicity of sangivamycin","volume":"6","author":"Taylor","year":"1987","journal-title":"Curr. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1021\/jm00369a010","article-title":"Antiviral activity of C-5 substituted tubercidin analogues","volume":"27","author":"Bergstrom","year":"1984","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1128\/AAC.29.3.482","article-title":"Antirhinovirus activity of purine nucleoside analogs","volume":"29","author":"Bernaerts","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0006-2952(80)90505-5","article-title":"Comparison between the inhibitory activities of sangivamycin and thiosangivamycin on nuclear ribonucleic acid synthesis in L1210 cells in vitro","volume":"29","author":"Glazer","year":"1980","journal-title":"Biochem. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S0021-9258(18)99293-8","article-title":"Pyrrolopyrimidine nucleotides and protein synthesis","volume":"243","author":"Uretsky","year":"1968","journal-title":"J. Biol. Chem."},{"key":"ref_70","first-page":"123ra24","article-title":"Productive replication of Ebola virus is regulated by the c-Abl1 tyrosine kinase","volume":"4","author":"Cooper","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.antiviral.2014.04.014","article-title":"Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells","volume":"107","author":"Johnson","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.antiviral.2015.05.003","article-title":"Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses","volume":"120","author":"Mohr","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Nelson, E.A., Dyall, J., Hoenen, T., Barnes, A.B., Zhou, H., Liang, J.Y., Michelotti, J., Dewey, W.H., DeWald, L.E., and Bennett, R.S. (2017). The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005540"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Stewart, C.M., Dorion, S.S., Ottenbrite, M.A.F., LeBlond, N.D., Smith, T.K.T., Qiu, S., Fullerton, M.D., Kobasa, D., and C\u00f4t\u00e9, M. (2019). A diacylglycerol kinase inhibitor, R-59-022, blocks filovirus internalization in host cells. Viruses, 11.","DOI":"10.3390\/v11030206"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Takamatsu, Y., Kr\u00e4hling, V., Kolesnikova, L., Halwe, S., Lier, C., Baumeister, S., Noda, T., Biedenkopf, N., and Becker, S. (2020). Serine-arginine protein kinase 1 regulates Ebola virus transcription. mBio, 11.","DOI":"10.1128\/mBio.02565-19"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20803","DOI":"10.1073\/pnas.2007837117","article-title":"Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2","volume":"117","author":"Kang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/cpt19701113","article-title":"The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man","volume":"11","author":"Schein","year":"1970","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_78","first-page":"1005","article-title":"The disposition of the antitumor agent, sangivamycin, in mice","volume":"34","author":"Hardesty","year":"1974","journal-title":"Cancer Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:23Z","timestamp":1760179703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,31]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010052"],"URL":"https:\/\/doi.org\/10.3390\/v13010052","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,31]]}}}