Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M
Abstract Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (W...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05817-w |
| _version_ | 1797836219478966272 |
|---|---|
| author | Elena Poggio Francesca Vallese Andreas J. W. Hartel Travis J. Morgenstern Scott A. Kanner Oliver Rauh Flavia Giamogante Lucia Barazzuol Kenneth L. Shepard Henry M. Colecraft Oliver Biggs Clarke Marisa Brini Tito Calì |
| author_facet | Elena Poggio Francesca Vallese Andreas J. W. Hartel Travis J. Morgenstern Scott A. Kanner Oliver Rauh Flavia Giamogante Lucia Barazzuol Kenneth L. Shepard Henry M. Colecraft Oliver Biggs Clarke Marisa Brini Tito Calì |
| author_sort | Elena Poggio |
| collection | DOAJ |
| description | Abstract Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited. |
| first_indexed | 2024-04-09T15:06:21Z |
| format | Article |
| id | doaj.art-6f24462f2be0478e821b38710e7c6258 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-09T15:06:21Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6f24462f2be0478e821b38710e7c62582023-04-30T11:30:02ZengNature Publishing GroupCell Death and Disease2041-48892023-04-0114411310.1038/s41419-023-05817-wPerturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and MElena Poggio0Francesca Vallese1Andreas J. W. Hartel2Travis J. Morgenstern3Scott A. Kanner4Oliver Rauh5Flavia Giamogante6Lucia Barazzuol7Kenneth L. Shepard8Henry M. Colecraft9Oliver Biggs Clarke10Marisa Brini11Tito Calì12Department of Biology, University of PadovaDepartment of Anesthesiology, Columbia University Irving Medical CenterDepartment of Electrical Engineering, Columbia UniversityDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical CenterDoctoral Program in Neurobiology and Behavior, Columbia University Vagelos College of Physicians and SurgeonsMembrane Biophysics, Department of Biology, Technical University of DarmstadtDepartment of Biomedical Sciences, University of PadovaDepartment of Biomedical Sciences, University of PadovaDepartment of Electrical Engineering, Columbia UniversityDepartment of Physiology and Cellular Biophysics, Columbia UniversityDepartment of Anesthesiology, Columbia University Irving Medical CenterDepartment of Biology, University of PadovaDepartment of Biomedical Sciences, University of PadovaAbstract Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.https://doi.org/10.1038/s41419-023-05817-w |
| spellingShingle | Elena Poggio Francesca Vallese Andreas J. W. Hartel Travis J. Morgenstern Scott A. Kanner Oliver Rauh Flavia Giamogante Lucia Barazzuol Kenneth L. Shepard Henry M. Colecraft Oliver Biggs Clarke Marisa Brini Tito Calì Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M Cell Death and Disease |
| title | Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M |
| title_full | Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M |
| title_fullStr | Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M |
| title_full_unstemmed | Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M |
| title_short | Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M |
| title_sort | perturbation of the host cell ca2 homeostasis and er mitochondria contact sites by the sars cov 2 structural proteins e and m |
| url | https://doi.org/10.1038/s41419-023-05817-w |
| work_keys_str_mv | AT elenapoggio perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT francescavallese perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT andreasjwhartel perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT travisjmorgenstern perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT scottakanner perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT oliverrauh perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT flaviagiamogante perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT luciabarazzuol perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT kennethlshepard perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT henrymcolecraft perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT oliverbiggsclarke perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT marisabrini perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm AT titocali perturbationofthehostcellca2homeostasisandermitochondriacontactsitesbythesarscov2structuralproteinseandm |