Small-Molecule Inhibition of Viral Fusion Glycoproteins.
antiviral
fusion inhibitor
inhibitor design
small molecule
viral fusion
Journal
Annual review of virology
ISSN: 2327-0578
Titre abrégé: Annu Rev Virol
Pays: United States
ID NLM: 101625721
Informations de publication
Date de publication:
29 09 2021
29 09 2021
Historique:
pubmed:
2
7
2021
medline:
5
3
2022
entrez:
1
7
2021
Statut:
ppublish
Résumé
Viral fusion glycoproteins catalyze membrane fusion during viral entry. Unlike most enzymes, however, they lack a conventional active site in which formation or scission of a specific covalent bond is catalyzed. Instead, they drive the membrane fusion reaction by cojoining highly regulated changes in conformation to membrane deformation. Despite the challenges in applying inhibitor design approaches to these proteins, recent advances in knowledge of the structures and mechanisms of viral fusogens have enabled the development of small-molecule inhibitors of both class I and class II viral fusion proteins. Here, we review well-validated inhibitors, including their discovery, targets, and mechanism(s) of action, while highlighting mechanistic similarities and differences. Together, these examples make a compelling case for small-molecule inhibitors as tools for probing the mechanisms of viral glycoprotein-mediated fusion and for viral glycoproteins as druggable targets.
Identifiants
pubmed: 34197186
doi: 10.1146/annurev-virology-022221-063725
pmc: PMC8543812
mid: NIHMS1743987
doi:
Substances chimiques
Viral Envelope Proteins
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-489Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146152
Pays : United States
Références
Antimicrob Agents Chemother. 2004 Nov;48(11):4349-59
pubmed: 15504864
Viruses. 2018 Nov 30;10(12):
pubmed: 30513600
J Med Chem. 2007 Sep 20;50(19):4572-84
pubmed: 17722899
EMBO J. 2004 Feb 25;23(4):728-38
pubmed: 14963486
Antiviral Res. 2009 Feb;81(2):132-40
pubmed: 19028526
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
J Virol. 2013 Sep;87(18):10255-62
pubmed: 23864626
ACS Chem Biol. 2008 Dec 19;3(12):765-75
pubmed: 19053243
Elife. 2018 Jul 12;7:
pubmed: 29999491
J Med Chem. 2008 Feb 28;51(4):875-96
pubmed: 18254606
J Virol. 2013 Jul;87(14):8017-28
pubmed: 23678171
Cell. 2002 Mar 8;108(5):717-25
pubmed: 11893341
Science. 2008 Mar 28;319(5871):1834-7
pubmed: 18369148
Science. 2008 Mar 28;319(5871):1830-4
pubmed: 18369147
J Virol. 2002 May;76(10):5266-70
pubmed: 11967340
Science. 2001 Feb 2;291(5505):884-8
pubmed: 11229405
Biochemistry. 1993 Mar 30;32(12):2967-78
pubmed: 8457561
J Virol. 1993 Nov;67(11):6642-7
pubmed: 7692082
Nature. 1981 Jan 29;289(5796):366-73
pubmed: 7464906
Nature. 2011 Aug 24;477(7364):340-3
pubmed: 21866103
J Med Virol. 2002 Oct;68(2):206-15
pubmed: 12210409
Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7154-9
pubmed: 27325770
Cell Chem Biol. 2018 Aug 16;25(8):1006-1016.e8
pubmed: 29937406
Nat Commun. 2017 Aug 1;8(1):167
pubmed: 28761099
Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18431-18438
pubmed: 32690700
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
mBio. 2016 Feb 23;7(1):e02154-15
pubmed: 26908579
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71
pubmed: 10535997
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15613-7
pubmed: 9861018
Cell Rep. 2013 Jan 31;3(1):30-5
pubmed: 23273918
Mol Cell. 1998 Nov;2(5):605-16
pubmed: 9844633
Antiviral Res. 2019 Apr;164:147-153
pubmed: 30771406
J Virol. 2003 May;77(9):5054-64
pubmed: 12692208
Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16828-33
pubmed: 17942675
AIDS Res Hum Retroviruses. 2001 Dec 10;17(18):1757-65
pubmed: 11788027
Nature. 2009 Feb 12;457(7231):882-6
pubmed: 19182773
Nature. 2012 Nov 15;491(7424):406-12
pubmed: 23151583
Elife. 2014 Nov 03;3:
pubmed: 25365453
Antiviral Res. 2003 Nov;60(3):209-19
pubmed: 14638397
Hepatology. 2016 Jan;63(1):49-62
pubmed: 26248546
Antimicrob Agents Chemother. 2004 Feb;48(2):413-22
pubmed: 14742189
mBio. 2020 Feb 11;11(1):
pubmed: 32047132
Cell. 2016 Jan 14;164(1-2):258-268
pubmed: 26771495
J Med Chem. 1999 Aug 26;42(17):3203-9
pubmed: 10464007
Nature. 2004 Jan 22;427(6972):320-5
pubmed: 14737160
EMBO J. 2002 Oct 1;21(19):5017-25
pubmed: 12356718
Sci Transl Med. 2015 Apr 8;7(282):282ra49
pubmed: 25855495
Cell. 1997 Apr 18;89(2):263-73
pubmed: 9108481
FEBS Lett. 1999 Dec 17;463(3):255-9
pubmed: 10606732
J Virol. 2007 Aug;81(16):8752-65
pubmed: 17537855
Virus Res. 2015 Apr 16;202:120-34
pubmed: 25445340
Virology. 2011 Oct 25;419(2):72-83
pubmed: 21907381
Nat Struct Biol. 1995 Dec;2(12):1075-82
pubmed: 8846219
Nat Rev Microbiol. 2013 Oct;11(10):688-700
pubmed: 24018384
Nat Chem Biol. 2020 May;16(5):529-537
pubmed: 32152540
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2496-2501
pubmed: 29463726
Proc Natl Acad Sci U S A. 1998 May 12;95(10):5762-7
pubmed: 9576958
Nature. 2016 Mar 3;531(7592):118-21
pubmed: 26935699
J Gen Virol. 2008 Feb;89(Pt 2):474-484
pubmed: 18198378
Antiviral Res. 2009 Dec;84(3):234-41
pubmed: 19781577
Nature. 2010 Dec 2;468(7324):709-12
pubmed: 21124458
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13703-13707
pubmed: 29203665
Antiviral Res. 2015 Dec;124:20-9
pubmed: 26515788
Nat Commun. 2014 Sep 16;5:4874
pubmed: 25224686
Biochim Biophys Acta. 2014 May;1838(5):1296-305
pubmed: 24388952
J Med Chem. 2006 Aug 24;49(17):5080-92
pubmed: 16913698
J Med Chem. 2018 Feb 8;61(3):724-733
pubmed: 29272110
J Virol. 2003 Mar;77(6):3647-54
pubmed: 12610140
Science. 2019 Mar 8;363(6431):
pubmed: 30846569
J Virol. 2012 Apr;86(8):4305-16
pubmed: 22318146
J Virol. 2006 Nov;80(22):11000-8
pubmed: 16943291
mBio. 2018 Jan 2;9(1):
pubmed: 29295909
Nature. 2006 Jan 5;439(7072):38-44
pubmed: 16397490
Nature. 1998 Jun 18;393(6686):648-59
pubmed: 9641677
Cell. 1993 May 21;73(4):823-32
pubmed: 8500173
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14172-7
pubmed: 11106388
J Virol. 2006 Apr;80(8):4174-8
pubmed: 16571833
J Virol. 2010 Jan;84(1):243-53
pubmed: 19846513
J Virol. 2002 Feb;76(4):1932-43
pubmed: 11799188
Antimicrob Agents Chemother. 2009 May;53(5):1823-31
pubmed: 19223625
J Virol. 2011 Apr;85(7):3106-19
pubmed: 21270170
Nat Microbiol. 2020 Dec;5(12):1532-1541
pubmed: 32868923
J Med Chem. 2017 Jul 27;60(14):6364-6383
pubmed: 28636348
Science. 2005 Jun 10;308(5728):1643-5
pubmed: 15831716
J Virol. 2006 Dec;80(23):11467-74
pubmed: 16987985
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91
pubmed: 12759475
EMBO J. 2003 Jun 2;22(11):2604-13
pubmed: 12773377
Proc Natl Acad Sci U S A. 1988 Nov;85(21):8052-6
pubmed: 3186706
Microbiol Mol Biol Rev. 2008 Mar;72(1):54-84, table of contents
pubmed: 18322034
Cell Chem Biol. 2016 Apr 21;23(4):443-52
pubmed: 27105280
Nature. 1994 Sep 1;371(6492):37-43
pubmed: 8072525
J Virol. 2005 Jan;79(2):1223-31
pubmed: 15613349
J Virol. 1997 Sep;71(9):7136-9
pubmed: 9261451
Science. 2014 Jun 27;344(6191):1506-10
pubmed: 24970085
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1696-701
pubmed: 23319635
Nature. 2008 Sep 4;455(7209):109-13
pubmed: 18668044
J Virol. 1999 Mar;73(3):2469-80
pubmed: 9971832
Antiviral Res. 2009 Dec;84(3):260-6
pubmed: 19800368
J Biol Chem. 1992 Oct 5;267(28):20225-32
pubmed: 1400340
Structure. 2004 Sep;12(9):1607-18
pubmed: 15341726
Nature. 2007 Apr 12;446(7137):801-5
pubmed: 17325668
mBio. 2019 Feb 19;10(1):
pubmed: 30782664
Nat Struct Mol Biol. 2008 Jul;15(7):690-8
pubmed: 18596815
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):206-214
pubmed: 28003465
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13938-43
pubmed: 16963566
Nature. 1997 May 22;387(6631):426-30
pubmed: 9163431
J Virol. 2006 Jul;80(14):6964-72
pubmed: 16809302
J Comput Aided Mol Des. 2009 Jun;23(6):333-41
pubmed: 19241120
J Virol. 2012 Dec;86(24):13407-22
pubmed: 23015720
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):308-13
pubmed: 19966279
Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8892-E8899
pubmed: 30185554
Cell. 1998 May 29;93(5):681-4
pubmed: 9630213
Nature. 2014 May 15;509(7500):381-4
pubmed: 24553139
Nature. 2004 Jan 22;427(6972):313-9
pubmed: 14737159
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41
pubmed: 19004788
Nature. 2010 Dec 2;468(7324):705-8
pubmed: 21124457
J Cell Biol. 2005 Oct 10;171(1):111-20
pubmed: 16216925
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15046-51
pubmed: 15469910
ACS Pharmacol Transl Sci. 2020 Oct 19;3(6):1165-1175
pubmed: 33330839
Nat Chem Biol. 2016 Feb;12(2):87-93
pubmed: 26641933
J Virol. 2003 Apr;77(8):4609-16
pubmed: 12663767
Antimicrob Agents Chemother. 2005 Sep;49(9):3755-61
pubmed: 16127050
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2375-9
pubmed: 18272496
Science. 2013 Nov 29;342(6162):1090-4
pubmed: 24288331
ACS Infect Dis. 2019 Mar 8;5(3):460-472
pubmed: 30608640
Annu Rev Biochem. 2000;69:531-69
pubmed: 10966468
Nat Rev Mol Cell Biol. 2003 Apr;4(4):309-19
pubmed: 12671653
Nat Chem Biol. 2006 Feb;2(2):95-102
pubmed: 16415863
J Pept Sci. 2015 May;21(5):379-86
pubmed: 25331523
Sci Transl Med. 2013 Jun 19;5(190):190ra79
pubmed: 23785035
Nature. 1992 Nov 26;360(6402):358-61
pubmed: 1360148
Virology. 2005 Dec 5;343(1):141-9
pubmed: 16168454
J Virol. 2000 May;74(10):4824-30
pubmed: 10775621
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6
pubmed: 9391135
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8
pubmed: 9356444
Virology. 2015 May;479-480:498-507
pubmed: 25866377
Nature. 2005 Feb 24;433(7028):834-41
pubmed: 15729334
Virology. 1997 Jun 9;232(2):281-90
pubmed: 9191841
Cell. 2001 Apr 6;105(1):137-48
pubmed: 11301009
J Med Chem. 2020 Jul 9;63(13):7211-7225
pubmed: 32490678
Antimicrob Agents Chemother. 2014;58(2):995-1004
pubmed: 24277038
J Biol Chem. 2011 Nov 4;286(44):37945-37954
pubmed: 21799008
Nature. 2016 Jul 7;535(7610):169-172
pubmed: 27362232
Nature. 2013 Jan 24;493(7433):552-6
pubmed: 23292515
J Virol. 2010 Dec;84(24):12549-54
pubmed: 20881042
ACS Infect Dis. 2018 Sep 14;4(9):1395-1406
pubmed: 30027735
Science. 1998 Oct 30;282(5390):938-41
pubmed: 9794763
Cell. 1985 Feb;40(2):431-9
pubmed: 3967299
Cell. 1999 Oct 1;99(1):103-15
pubmed: 10520998
J Biomed Sci. 2009 Sep 24;16:89
pubmed: 19778418
Cell Chem Biol. 2020 Jul 16;27(7):780-792.e5
pubmed: 32386595
J Med Chem. 2009 Jul 23;52(14):4257-65
pubmed: 19499921
Antimicrob Agents Chemother. 2010 Oct;54(10):4487-92
pubmed: 20643898
Virology. 2003 Mar 15;307(2):255-65
pubmed: 12667795
Virology. 1991 Mar;181(1):70-7
pubmed: 1704661
Nature. 1995 May 25;375(6529):291-8
pubmed: 7753193
Nat Med. 2009 Nov;15(11):1251-2
pubmed: 19893556
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5628-33
pubmed: 15056763
J Virol. 2019 Jul 17;93(15):
pubmed: 31092576
J Med Chem. 2015 Feb 26;58(4):1630-43
pubmed: 25574686
PLoS Pathog. 2010 Apr 08;6(4):e1000851
pubmed: 20386713
Science. 2013 Nov 1;342(6158):592-8
pubmed: 24179220
Antimicrob Agents Chemother. 2009 Dec;53(12):4987-98
pubmed: 19786602
J Virol. 1997 Nov;71(11):8808-20
pubmed: 9343241