SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights
Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed of four structural proteins and several accessory non-structural proteins. SARS-CoV-2’s most abundant structural protein, Membrane (M) protein, has a pivotal role both during viral infection cycle and host interferon antagonism...
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MDPI AG
2022-03-01
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author | Catarina Marques-Pereira Manuel N. Pires Raquel P. Gouveia Nádia N. Pereira Ana B. Caniceiro Nícia Rosário-Ferreira Irina S. Moreira |
author_facet | Catarina Marques-Pereira Manuel N. Pires Raquel P. Gouveia Nádia N. Pereira Ana B. Caniceiro Nícia Rosário-Ferreira Irina S. Moreira |
author_sort | Catarina Marques-Pereira |
collection | DOAJ |
description | Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed of four structural proteins and several accessory non-structural proteins. SARS-CoV-2’s most abundant structural protein, Membrane (M) protein, has a pivotal role both during viral infection cycle and host interferon antagonism. This is a highly conserved viral protein, thus an interesting and suitable target for drug discovery. In this paper, we explain the structural nature of M protein homodimer. To do so, we developed and applied a detailed and robust in silico workflow to predict M protein dimeric structure, membrane orientation, and interface characterization. Single Nucleotide Polymorphisms (SNPs) in M protein were retrieved from over 1.2 M SARS-CoV-2 genomes and proteins from the Global Initiative on Sharing All Influenza Data (GISAID) database, 91 of which were located at the predicted dimer interface. Among those, we identified SNPs in Variants of Concern (VOC) and Variants of Interest (VOI). Binding free energy differences were evaluated for dimer interfacial SNPs to infer mutant protein stabilities. A few high-prevalent mutated residues were found to be especially relevant in VOC and VOI. This realization may be a game-changer to structure-driven formulation of new therapeutics for SARS-CoV-2. |
first_indexed | 2024-03-09T19:43:37Z |
format | Article |
id | doaj.art-b4a20a06be1b4b7d9d956b66846d4172 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T19:43:37Z |
publishDate | 2022-03-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-b4a20a06be1b4b7d9d956b66846d41722023-11-24T01:30:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236298610.3390/ijms23062986SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New InsightsCatarina Marques-Pereira0Manuel N. Pires1Raquel P. Gouveia2Nádia N. Pereira3Ana B. Caniceiro4Nícia Rosário-Ferreira5Irina S. Moreira6CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-535 Coimbra, PortugalDepartment of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, PortugalSevere Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed of four structural proteins and several accessory non-structural proteins. SARS-CoV-2’s most abundant structural protein, Membrane (M) protein, has a pivotal role both during viral infection cycle and host interferon antagonism. This is a highly conserved viral protein, thus an interesting and suitable target for drug discovery. In this paper, we explain the structural nature of M protein homodimer. To do so, we developed and applied a detailed and robust in silico workflow to predict M protein dimeric structure, membrane orientation, and interface characterization. Single Nucleotide Polymorphisms (SNPs) in M protein were retrieved from over 1.2 M SARS-CoV-2 genomes and proteins from the Global Initiative on Sharing All Influenza Data (GISAID) database, 91 of which were located at the predicted dimer interface. Among those, we identified SNPs in Variants of Concern (VOC) and Variants of Interest (VOI). Binding free energy differences were evaluated for dimer interfacial SNPs to infer mutant protein stabilities. A few high-prevalent mutated residues were found to be especially relevant in VOC and VOI. This realization may be a game-changer to structure-driven formulation of new therapeutics for SARS-CoV-2.https://www.mdpi.com/1422-0067/23/6/2986SARS-CoV-2genomicsproteomics |
spellingShingle | Catarina Marques-Pereira Manuel N. Pires Raquel P. Gouveia Nádia N. Pereira Ana B. Caniceiro Nícia Rosário-Ferreira Irina S. Moreira SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights International Journal of Molecular Sciences SARS-CoV-2 genomics proteomics |
title | SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights |
title_full | SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights |
title_fullStr | SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights |
title_full_unstemmed | SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights |
title_short | SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights |
title_sort | sars cov 2 membrane protein from genomic data to structural new insights |
topic | SARS-CoV-2 genomics proteomics |
url | https://www.mdpi.com/1422-0067/23/6/2986 |
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