{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:49:09Z","timestamp":1791413349220,"version":"4.3.3"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral\/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV\/MARV therapy.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV\/MARV therapy.\n          <\/jats:p>","DOI":"10.1128\/jvi.01337-15","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T01:20:03Z","timestamp":1437614403000},"page":"9932-9938","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists"],"prefix":"10.1128","volume":"89","author":[{"given":"Han","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calli M.","family":"Lear-Rooney","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Johansen","sequence":"additional","affiliation":[{"name":"Horizon Discovery Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Varhegyi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng W.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene G.","family":"Olinger","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"923","volume-title":"Fields virology","author":"Feldmann F","year":"2013","unstructured":"Feldmann F, Sanchez A, Geisbert JB. 2013. Filoviridae: Marburg and Ebola viruses, p 923\u2013956. In Knipe DM, Howley PM (ed), Fields virology, 6th ed, vol II. Wolters Kluwer Lippincott Willliams & Wilkins, Philadelphia, PA.","edition":"6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/438575a"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13777"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01876"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13027"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03689-14"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01621-12"},{"key":"e_1_3_3_9_2","volume-title":"R: a language and environment for statistical computing","author":"Team RDC","year":"2011","unstructured":"Team RDC. 2011. R: a language and environment for statistical computing. 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