A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19
The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/10/12/1276 |
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| author | Andrei Lobiuc Daniel Șterbuleac Olga Sturdza Mihai Dimian Mihai Covasa |
| author_facet | Andrei Lobiuc Daniel Șterbuleac Olga Sturdza Mihai Dimian Mihai Covasa |
| author_sort | Andrei Lobiuc |
| collection | DOAJ |
| description | The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease. |
| first_indexed | 2024-03-10T04:34:35Z |
| format | Article |
| id | doaj.art-4895732dd87d42ab9a34053344bdf189 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T04:34:35Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-4895732dd87d42ab9a34053344bdf1892023-11-23T03:53:34ZengMDPI AGBiology2079-77372021-12-011012127610.3390/biology10121276A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19Andrei Lobiuc0Daniel Șterbuleac1Olga Sturdza2Mihai Dimian3Mihai Covasa4Department of Biomedical Sciences, College of Medicine and Biological Sciences, “Ștefan cel Mare” University of Suceava, Str. Universității 13, 720229 Suceava, RomaniaDepartment of Biomedical Sciences, College of Medicine and Biological Sciences, “Ștefan cel Mare” University of Suceava, Str. Universității 13, 720229 Suceava, RomaniaDepartment of Biomedical Sciences, College of Medicine and Biological Sciences, “Ștefan cel Mare” University of Suceava, Str. Universității 13, 720229 Suceava, RomaniaIntegrated Center for Research, Development and Innovation in Advanced Materials, Nanotechnologies and Distributed Systems for Fabrication and Control (MANSiD), “Ștefan cel Mare” University of Suceava, Str. Universității 13, 720229 Suceava, RomaniaDepartment of Biomedical Sciences, College of Medicine and Biological Sciences, “Ștefan cel Mare” University of Suceava, Str. Universității 13, 720229 Suceava, RomaniaThe ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69–70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.https://www.mdpi.com/2079-7737/10/12/1276molecular dynamicsORF7aprotein modelingRMSFviral mutation |
| spellingShingle | Andrei Lobiuc Daniel Șterbuleac Olga Sturdza Mihai Dimian Mihai Covasa A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 Biology molecular dynamics ORF7a protein modeling RMSF viral mutation |
| title | A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 |
| title_full | A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 |
| title_fullStr | A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 |
| title_full_unstemmed | A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 |
| title_short | A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19 |
| title_sort | conservative replacement in the transmembrane domain of sars cov 2 orf7a as a putative risk factor in covid 19 |
| topic | molecular dynamics ORF7a protein modeling RMSF viral mutation |
| url | https://www.mdpi.com/2079-7737/10/12/1276 |
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