Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer

Bibliographic Details
Title: Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer
Authors: Niayesh Razi, Weizhong Li, Maxinne A. Ignacio, Jeffrey M. Loube, Eva L. Agostino, Xiaoping Zhu, Margaret A. Scull, Jeffrey J. DeStefano
Source: Respiratory Research, Vol 24, Iss 1, Pp 1-11 (2023)
Publisher Information: BMC, 2023.
Publication Year: 2023
Collection: LCC:Diseases of the respiratory system
Subject Terms: FANA, Aptamer, SARS-CoV-2, Human airway epithelium, Diseases of the respiratory system, RC705-779
More Details: Abstract Background SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. Methods Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. Results We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. Conclusions Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1465-993X
Relation: https://doaj.org/toc/1465-993X
DOI: 10.1186/s12931-023-02590-4
Access URL: https://doaj.org/article/b7423d2e95a8442f8391cf82c24054b9
Accession Number: edsdoj.b7423d2e95a8442f8391cf82c24054b9
Database: Directory of Open Access Journals
More Details
ISSN:1465993X
DOI:10.1186/s12931-023-02590-4
Published in:Respiratory Research
Language:English