Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets.
Administration, Intranasal
Animals
COVID-19
/ prevention & control
Chlorocebus aethiops
Disease Models, Animal
Drug Design
Ferrets
Lipopeptides
/ administration & dosage
Membrane Fusion
/ drug effects
Mice
Pre-Exposure Prophylaxis
SARS-CoV-2
/ drug effects
Spike Glycoprotein, Coronavirus
/ metabolism
Tissue Distribution
Vero Cells
Viral Fusion Protein Inhibitors
/ administration & dosage
Virus Internalization
/ drug effects
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
26 03 2021
26 03 2021
Historique:
received:
29
10
2020
revised:
04
01
2021
accepted:
09
02
2021
pubmed:
19
2
2021
medline:
13
4
2021
entrez:
18
2
2021
Statut:
ppublish
Résumé
Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.
Identifiants
pubmed: 33597220
pii: science.abf4896
doi: 10.1126/science.abf4896
pmc: PMC8011693
doi:
Substances chimiques
Lipopeptides
0
Spike Glycoprotein, Coronavirus
0
Viral Fusion Protein Inhibitors
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1379-1382Subventions
Organisme : NIAID NIH HHS
ID : R56 AI146980
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL120826
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114736
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121349
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091263
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Elife. 2021 Jan 04;10:
pubmed: 33393462
Cell Res. 2020 Apr;30(4):343-355
pubmed: 32231345
Euro Surveill. 2020 Jan;25(3):
pubmed: 31992387
Annu Rev Virol. 2016 Sep 29;3(1):237-261
pubmed: 27578435
Nat Commun. 2020 Jul 8;11(1):3496
pubmed: 32641684
Int J Mol Sci. 2020 May 28;21(11):
pubmed: 32481690
Science. 2021 Mar 12;371(6534):1152-1153
pubmed: 33514629
J Virol. 2020 Mar 17;94(7):
pubmed: 31996437
Sci Adv. 2019 Apr 10;5(4):eaav4580
pubmed: 30989115
PLoS One. 2012;7(5):e36833
pubmed: 22666328
Nature. 2003 Oct 30;425(6961):915
pubmed: 14586458
J Virol. 2016 Dec 16;91(1):
pubmed: 27733647
J Phys Chem B. 2007 Jul 12;111(27):7812-24
pubmed: 17569554
J Virol. 2020 Jul 1;94(14):
pubmed: 32376627
Nat Commun. 2020 Nov 26;11(1):6013
pubmed: 33243994
ACS Nano. 2018 Oct 23;12(10):9855-9865
pubmed: 30230818
Science. 2020 Sep 25;369(6511):1586-1592
pubmed: 32694201
Bioconjug Chem. 2018 Oct 17;29(10):3362-3376
pubmed: 30169965
PLoS Pathog. 2010 Oct 28;6(10):e1001168
pubmed: 21060819
Cell Host Microbe. 2020 May 13;27(5):704-709.e2
pubmed: 32259477
Nat Microbiol. 2021 Jan;6(1):11-18
pubmed: 33273742
mBio. 2020 Oct 20;11(5):
pubmed: 33082259
Science. 2020 Oct 23;370(6515):426-431
pubmed: 32907861
Sci Rep. 2017 Mar 08;7:43610
pubmed: 28344321
Nature. 2020 Sep;585(7826):588-590
pubmed: 32698190
J Chem Theory Comput. 2012 Sep 11;8(9):3257-3273
pubmed: 23341755
J Med Virol. 2007 Dec;79(12):1868-76
pubmed: 17935176
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Science. 2020 Dec 18;370(6523):1473-1479
pubmed: 33154106
Science. 2009 Jul 24;325(5939):481-3
pubmed: 19574348
J Biol Chem. 2006 Apr 28;281(17):11965-71
pubmed: 16507566