دورية أكاديمية
أعرض في EDS

Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications.

التفاصيل البيبلوغرافية
العنوان: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications.
المؤلفون: Nelson EA; Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA. en2b@virginia.edu., Barnes AB; Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA. abb9uu@virginia.edu., Wiehle RD; Repros Therapeutics, Inc., The Woodlands, TX 77380, USA. rwiehle@reprosrx.com., Fontenot GK; Repros Therapeutics, Inc., The Woodlands, TX 77380, USA. GFontenot@reprosrx.com., Hoenen T; Laboratory of Virology, Division of Intramural Research, National Institutes of Health, Hamilton, MT 59840, USA. thomas.hoenen@fli.bund.de.; Friedrich-Loeffler-Institut, D-17493, Greifswald-Insel Riems, Germany. thomas.hoenen@fli.bund.de., White JM; Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA. jw7g@virginia.edu.
المصدر: Viruses [Viruses] 2016 Aug 02; Vol. 8 (8). Date of Electronic Publication: 2016 Aug 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Intramural; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Antiviral Agents/*pharmacology , Clomiphene/*pharmacology , Ebolavirus/*drug effects , Ebolavirus/*physiology , Selective Estrogen Receptor Modulators/*pharmacology , Virus Internalization/*drug effects, Animals ; Cell Line ; Hemorrhagic Fever, Ebola/drug therapy ; Humans ; Zuclomiphene/pharmacology
مستخلص: The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.
References: Biol Reprod. 1981 Oct;25(3):667-72. (PMID: 7197996)
Nature. 2015 May 21;521(7552):362-5. (PMID: 25901685)
Sci Transl Med. 2015 Jun 3;7(290):290ra89. (PMID: 26041706)
Lancet Glob Health. 2014 Dec;2(12):e686. (PMID: 25433619)
Sci Transl Med. 2013 Jun 19;5(190):190ra79. (PMID: 23785035)
Nature. 2014 Oct 2;514(7520):47-53. (PMID: 25171469)
J Virol. 2015 Mar;89(5):2931-43. (PMID: 25552710)
PLoS One. 2013;8(4):e60579. (PMID: 23577127)
PLoS Pathog. 2015 Nov 12;11(11):e1005221. (PMID: 26562671)
Sci Rep. 2016 Feb 10;6:20514. (PMID: 26861827)
N Engl J Med. 2015 Oct 14;:null. (PMID: 26465681)
MBio. 2016 Feb 09;7(1):e01857-15. (PMID: 26861015)
FASEB J. 2008 Mar;22(3):659-61. (PMID: 17942826)
Science. 2016 Mar 18;351(6279):1339-42. (PMID: 26917593)
Hum Reprod Update. 1996 Nov-Dec;2(6):483-506. (PMID: 9111183)
Antiviral Res. 2014 May;105:17-21. (PMID: 24583123)
Fertil Steril. 1986 Sep;46(3):392-6. (PMID: 3091405)
N Engl J Med. 2015 Dec 17;373(25):2448-54. (PMID: 26465384)
Fertil Steril. 2010 Dec;94(7):2659-64. (PMID: 20451181)
Nature. 2014 Apr 17;508(7496):402-5. (PMID: 24590073)
Fertil Steril. 1999 Apr;71(4):639-44. (PMID: 10202872)
BJU Int. 2013 Jul 12;:null. (PMID: 23875626)
J Virol. 2015 Oct;89(19):9932-8. (PMID: 26202243)
J Vis Exp. 2014 Sep 27;(91):52381. (PMID: 25285674)
Urology. 1991 Oct;38(4):317-22. (PMID: 1755138)
J Virol. 2015 Oct 14;90(1):605-10. (PMID: 26468524)
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5034-9. (PMID: 22411795)
N Engl J Med. 2015 Jun 18;372(25):2423-7. (PMID: 25950269)
Lancet Infect Dis. 2015 Aug;15(8):905-12. (PMID: 25910637)
Br J Clin Pharmacol. 1989 May;27(5):639-40. (PMID: 2757886)
Cochrane Database Syst Rev. 2000;(2):CD000056. (PMID: 10796477)
Expert Opin Investig Drugs. 2009 Dec;18(12):1947-55. (PMID: 19938905)
J Virol. 2014 Sep;88(18):10511-24. (PMID: 24965473)
Endocrinology. 1999 Sep;140(9):3928-37. (PMID: 10465261)
BJU Int. 2016 Feb;117(2):344-50. (PMID: 26220499)
MBio. 2015 May 26;6(3):e00565-15. (PMID: 26015498)
J Clin Pharmacol. 2009 Feb;49(2):147-54. (PMID: 19033451)
Hum Mol Genet. 2012 Mar 1;21(5):1145-54. (PMID: 22108178)
PLoS One. 2013;8(2):e56265. (PMID: 23441171)
Fertil Steril. 2004 May;81(5):1187-93. (PMID: 15136073)
Nature. 2016 Mar 17;531(7594):381-5. (PMID: 26934220)
Emerg Microbes Infect. 2014 Dec;3(12):e84. (PMID: 26038505)
Science. 2014 Jul 25;345(6195):364-5. (PMID: 25061181)
Science. 2016 Mar 4;351(6277):1078-83. (PMID: 26912366)
Science. 2016 Mar 18;351(6279):1343-6. (PMID: 26917592)
معلومات مُعتمدة: R01 AI114776 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: Ebola; Ebola Virus disease; Ebola virus survivors; anti-viral; enclomiphene; filovirus; zuclomiphene
المشرفين على المادة: 0 (Antiviral Agents)
0 (Selective Estrogen Receptor Modulators)
1HRS458QU2 (Clomiphene)
3JU1DU3652 (Zuclomiphene)
تواريخ الأحداث: Date Created: 20160805 Date Completed: 20170926 Latest Revision: 20181113
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4997570
DOI: 10.3390/v8080206
PMID: 27490565
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v8080206