SARS-CoV-2 strategically mimics proteolytic activation of human ENaC.
Elife
; 92020 05 26.
Article
em En
| MEDLINE
| ID: mdl-32452762
Viruses hijack the cellular machinery of humans to infect their cells and multiply. The virus causing the global COVID-19 pandemic, SARS-CoV-2, is no exception. Identifying which proteins in human cells the virus co-opts is crucial for developing new ways to diagnose, prevent and treat COVID-19 infections. SARS-CoV-2 is covered in spike-shaped proteins, which the virus uses to gain entry into cells. First, the spikes bind to a protein called ACE2, which is found on the cells that line the respiratory tract and lungs. SARS-CoV-2 then exploits enzymes called proteases to cut, or cleave, its spikes at a specific site which allows the virus to infiltrate the host cell. Proteases identify which proteins to target based on the sequence of amino acids the building blocks of proteins at the cleavage site. However, it remained unclear which human proteases SARS-CoV-2 co-opts and whether its cut site is similar to human proteins. Now, Anand et al. show that the spike proteins on SARS-CoV-2 may have the same sequence of amino acids at its cut site as a human epithelial channel protein called ENaC-α. This channel is important for maintaining the balance of salt and water in many organs including the lungs. Further analyses showed that ENaC-α is often found in the same types of human lung and respiratory tract cells as ACE2. This suggests that SARS-CoV-2 may use the same proteases that cut ENaC-α to get inside human respiratory cells. It is possible that by hijacking the cutting mechanism for ENaC-α, SARS-CoV-2 interferes with the balance of salt and water in the lungs of COVID-19 patients. This may help explain why the virus causes severe respiratory symptoms. However, more studies are needed to confirm that the proteases that cut ENaC-α also cut the spike proteins on SARS-CoV-2, and how this affects the respiratory health of COVID-19 patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
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Pneumonia Viral
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Proteínas Virais
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Proteínas do Envelope Viral
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Infecções por Coronavirus
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Mimetismo Molecular
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Canais Epiteliais de Sódio
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Betacoronavirus
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article