DNA aptamers masking angiotensin converting enzyme 2 as an innovative way to treat SARS-CoV-2 pandemic.
A549 Cells
Angiotensin-Converting Enzyme 2
/ antagonists & inhibitors
Aptamers, Nucleotide
/ genetics
COVID-19
/ enzymology
HEK293 Cells
Host-Pathogen Interactions
Humans
Mutation
Receptors, Virus
/ antagonists & inhibitors
SARS-CoV-2
/ genetics
SELEX Aptamer Technique
Virus Internalization
/ drug effects
COVID-19 Drug Treatment
ACE2
COVID-19 therapy
Coronavirus
Nucleic acid-based drugs
SARS-CoV-2 variants
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
14
07
2021
revised:
09
11
2021
accepted:
09
11
2021
pubmed:
20
11
2021
medline:
20
1
2022
entrez:
19
11
2021
Statut:
ppublish
Résumé
All the different coronavirus SARS-CoV-2 variants isolated so far share the same mechanism of infection mediated by the interaction of their spike (S) glycoprotein with specific residues on their cellular receptor: the angiotensin converting enzyme 2 (ACE2). Therefore, the steric hindrance on this cellular receptor created by a bulk macromolecule may represent an effective strategy for the prevention of the viral spreading and the onset of severe forms of Corona Virus disease 19 (COVID-19). Here, we applied a systematic evolution of ligands by exponential enrichment (SELEX) procedure to identify two single strand DNA molecules (aptamers) binding specifically to the region surrounding the K353, the key residue in human ACE2 interacting with the N501 amino acid of the SARS-CoV-2 S. 3D docking in silico experiments and biochemical assays demonstrated that these aptamers bind to this region, efficiently prevent the SARS-CoV-2 S/human ACE2 interaction and the viral infection in the nanomolar range, regardless of the viral variant, thus suggesting the possible clinical development of these aptamers as SARS-CoV-2 infection inhibitors. Our approach brings a significant innovation to the therapeutic paradigm of the SARS-CoV-2 pandemic by protecting the target cell instead of focusing on the virus; this is particularly attractive in light of the increasing number of viral mutants that may potentially escape the currently developed immune-mediated neutralization strategies.
Identifiants
pubmed: 34798263
pii: S1043-6618(21)00566-1
doi: 10.1016/j.phrs.2021.105982
pmc: PMC8594078
pii:
doi:
Substances chimiques
Aptamers, Nucleotide
0
Receptors, Virus
0
ACE2 protein, human
EC 3.4.17.23
Ace2 protein, mouse
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105982Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Références
Engineering (Beijing). 2020 Oct;6(10):1099-1107
pubmed: 33520331
J Mol Biol. 2016 Feb 22;428(4):720-725
pubmed: 26410586
J Clin Invest. 2021 Apr 1;131(7):
pubmed: 33621214
Lancet Infect Dis. 2020 Apr;20(4):400-402
pubmed: 32113509
Proc Natl Acad Sci U S A. 2021 Feb 23;118(8):
pubmed: 33597292
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Crit Care Med. 2020 Dec;48(12):e1350-e1355
pubmed: 32833695
N Engl J Med. 2021 Feb 11;384(6):497-511
pubmed: 33264556
Cell. 2021 Apr 1;184(7):1821-1835.e16
pubmed: 33667349
Cell Death Differ. 2021 Feb;28(2):626-639
pubmed: 33479399
Chem Commun (Camb). 2021 Apr 4;57(26):3283-3286
pubmed: 33651072
Mol Ther. 2022 Jan 5;30(1):311-326
pubmed: 34547465
J Virol. 2020 Aug 31;94(18):
pubmed: 32661139
Sci Data. 2020 Sep 16;7(1):309
pubmed: 32938937
Pharmacol Res. 2020 Jun;156:104761
pubmed: 32205232
Cell. 2021 Apr 29;184(9):2316-2331.e15
pubmed: 33773105
Nat Commun. 2020 Sep 11;11(1):4541
pubmed: 32917884
Arch Virol. 2021 Mar;166(3):697-714
pubmed: 33483791
Nature. 2020 May;581(7809):465-469
pubmed: 32235945
Intensive Care Med. 2020 Apr;46(4):586-590
pubmed: 32125455
BMJ. 2021 Mar 9;372:n579
pubmed: 33687922
Science. 1990 Aug 3;249(4968):505-10
pubmed: 2200121
Nature. 2020 May;581(7807):221-224
pubmed: 32225175
Nat Commun. 2021 Jan 12;12(1):288
pubmed: 33436577
Science. 2021 Apr 9;372(6538):
pubmed: 33658326
Anal Chem. 2020 Jul 21;92(14):9895-9900
pubmed: 32551560
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W235-9
pubmed: 19417072
N Engl J Med. 2021 May 13;384(19):1866-1868
pubmed: 33761203
Nat Med. 2021 May;27(5):917-924
pubmed: 33772244
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
pubmed: 12824337
Pharmacol Res. 2020 Aug;158:104939
pubmed: 32445956
Antimicrob Agents Chemother. 2005 Nov;49(11):4721-32
pubmed: 16251317
Science. 2005 Sep 16;309(5742):1864-8
pubmed: 16166518
Viruses. 2021 Jul 02;13(7):
pubmed: 34372498
Geroscience. 2020 Aug;42(4):1021-1049
pubmed: 32430627
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Expert Rev Respir Med. 2020 Sep;14(9):865-868
pubmed: 32567404
J Cell Physiol. 2021 Oct;236(10):7045-7057
pubmed: 33755190
Nat Med. 2021 Apr;27(4):717-726
pubmed: 33664494
J Biol Chem. 2004 Apr 23;279(17):17996-8007
pubmed: 14754895
Heart Fail Rev. 2021 Mar;26(2):371-380
pubmed: 32844337
Pharmacol Res. 2021 Jun;168:105581
pubmed: 33781873
JAMA. 2021 Apr 6;325(13):1261-1262
pubmed: 33571363
Int J Mol Sci. 2017 Oct 14;18(10):
pubmed: 29036890
J Clin Pathol. 2021 May;74(5):285-290
pubmed: 32759311
Pharmacol Res. 2020 Nov;161:105290
pubmed: 33181320
Nat Rev Drug Discov. 2017 Mar;16(3):181-202
pubmed: 27807347
Anaesthesia. 2021 May;76(5):608-616
pubmed: 33572007
Curr Opin Chem Biol. 2008 Aug;12(4):448-56
pubmed: 18644461
Pharmacol Res. 2020 Feb;152:104550
pubmed: 31866285
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
Nature. 2021 May;593(7857):130-135
pubmed: 33684923
Wellcome Open Res. 2020 Jul 29;5:181
pubmed: 33283055
Hum Genomics. 2021 Feb 3;15(1):10
pubmed: 33536081
Blood. 2020 Oct 15;136(16):1888-1891
pubmed: 32871595
J Chem Theory Comput. 2014 Oct 14;10(10):4745-58
pubmed: 26588162