DNA aptamers masking angiotensin converting enzyme 2 as an innovative way to treat SARS-CoV-2 pandemic.
Pharmacol Res
; 175: 105982, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1527828
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, Virus
/
Aptamers, Nucleotide
/
Virus Internalization
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
/
Systematic review/Meta Analysis
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Pharmacol Res
Journal subject:
Pharmacology
Year:
2022
Document Type:
Article
Affiliation country:
J.phrs.2021.105982
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