In Vivo protection from SARS-CoV-2 infection by ATN-161 in k18-hACE2 transgenic mice.
Life Sci
; 284: 119881, 2021 Nov 01.
Article
in English
| MEDLINE | ID: covidwho-1347741
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5ß1, and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin α5ß1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 h after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence, and improved lung histology in a majority of mice 72 h post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin α5 and αv (an α5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C-X-C motif chemokine ligand 10 (Cxcl10), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin α5ß1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Oligopeptides
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Life Sci
Year:
2021
Document Type:
Article
Affiliation country:
J.lfs.2021.119881
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