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SARS-CoV-2 Nsp6-Omicron causes less damage to the Drosophila heart and mouse cardiomyocytes than ancestral Nsp6.
- Source :
-
Communications biology [Commun Biol] 2024 Dec 03; Vol. 7 (1), pp. 1609. Date of Electronic Publication: 2024 Dec 03. - Publication Year :
- 2024
-
Abstract
- A few years into the COVID-19 pandemic, the SARS-CoV-2 Omicron strain rapidly becomes and has remained the predominant strain. To date, Omicron and its subvariants, while more transmittable, appear to cause less severe disease than prior strains. To study the cause of this reduced pathogenicity we compare SARS-CoV-2 ancestral Nsp6 with Nsp6-Omicron, which we have previously identified as one of the most pathogenic viral proteins. Here, through ubiquitous expression in Drosophila, we show that ancestral Nsp6 causes both structural and functional damage to cardiac, muscular, and tracheal (lung) tissue, whereas Nsp6-Omicron has minimal effects. Moreover, we show that ancestral Nsp6 dysregulates the glycolysis pathway and disrupts mitochondrial function, whereas Nsp6-Omicron does not. Through validation in mouse primary cardiomyocytes, we find that Nsp6-induced dysregulated glycolysis underlies the cardiac dysfunction. Together, the results indicate that the amino acid changes in Omicron might hinder its interaction with host proteins thereby minimizing its pathogenicity.<br />Competing Interests: Competing interests: The authors declare no competing interests.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
COVID-19 virology
COVID-19 metabolism
COVID-19 pathology
Glycolysis
Drosophila virology
Drosophila genetics
Drosophila melanogaster virology
Drosophila melanogaster genetics
Drosophila melanogaster metabolism
Humans
Myocytes, Cardiac virology
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
SARS-CoV-2 pathogenicity
SARS-CoV-2 genetics
Viral Nonstructural Proteins metabolism
Viral Nonstructural Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 39627475
- Full Text :
- https://doi.org/10.1038/s42003-024-07307-x