Cargando…
The zinc proteome of SARS-CoV-2
Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314716/ https://www.ncbi.nlm.nih.gov/pubmed/35767875 http://dx.doi.org/10.1093/mtomcs/mfac047 |
_version_ | 1784754384158064640 |
---|---|
author | Andreini, Claudia Arnesano, Fabio Rosato, Antonio |
author_facet | Andreini, Claudia Arnesano, Fabio Rosato, Antonio |
author_sort | Andreini, Claudia |
collection | PubMed |
description | Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that zinc(II) is the most common metal ion that binds to viral proteins. However, the number of zinc(II)-binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc(II)-binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc(II) sites were identified and a further 22 were predicted in Spike, open reading frame (ORF)3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc(II) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites (typically zinc fingers) indicate that SARS-CoV-2 can compete with human proteins for zinc(II) binding. Given the double-edged effect of zinc(II) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc(II)-binding sites can guide selective antiviral strategies based on zinc supplementation. |
format | Online Article Text |
id | pubmed-9314716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93147162022-07-26 The zinc proteome of SARS-CoV-2 Andreini, Claudia Arnesano, Fabio Rosato, Antonio Metallomics Paper Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that zinc(II) is the most common metal ion that binds to viral proteins. However, the number of zinc(II)-binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc(II)-binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc(II) sites were identified and a further 22 were predicted in Spike, open reading frame (ORF)3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc(II) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites (typically zinc fingers) indicate that SARS-CoV-2 can compete with human proteins for zinc(II) binding. Given the double-edged effect of zinc(II) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc(II)-binding sites can guide selective antiviral strategies based on zinc supplementation. Oxford University Press 2022-06-29 /pmc/articles/PMC9314716/ /pubmed/35767875 http://dx.doi.org/10.1093/mtomcs/mfac047 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Paper Andreini, Claudia Arnesano, Fabio Rosato, Antonio The zinc proteome of SARS-CoV-2 |
title | The zinc proteome of SARS-CoV-2 |
title_full | The zinc proteome of SARS-CoV-2 |
title_fullStr | The zinc proteome of SARS-CoV-2 |
title_full_unstemmed | The zinc proteome of SARS-CoV-2 |
title_short | The zinc proteome of SARS-CoV-2 |
title_sort | zinc proteome of sars-cov-2 |
topic | Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314716/ https://www.ncbi.nlm.nih.gov/pubmed/35767875 http://dx.doi.org/10.1093/mtomcs/mfac047 |
work_keys_str_mv | AT andreiniclaudia thezincproteomeofsarscov2 AT arnesanofabio thezincproteomeofsarscov2 AT rosatoantonio thezincproteomeofsarscov2 AT andreiniclaudia zincproteomeofsarscov2 AT arnesanofabio zincproteomeofsarscov2 AT rosatoantonio zincproteomeofsarscov2 |