A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions
Several more infectious SARS-CoV-2 variants have emerged globally since SARS-CoV-2 pandemic and the discovery of the first D614G variant of SARS-CoV-2 spike proteins in 2020. Delta (B.1.617.2) and Omicron (B.1.1.529) variants have proven to be of major concern out of all the reported variants, consi...
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| Language: | English |
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Elsevier
2022-01-01
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| Series: | Informatics in Medicine Unlocked |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914822002106 |
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| author | Kehinde A. Idowu Collins Onyenaka Omonike A. Olaleye |
| author_facet | Kehinde A. Idowu Collins Onyenaka Omonike A. Olaleye |
| author_sort | Kehinde A. Idowu |
| collection | DOAJ |
| description | Several more infectious SARS-CoV-2 variants have emerged globally since SARS-CoV-2 pandemic and the discovery of the first D614G variant of SARS-CoV-2 spike proteins in 2020. Delta (B.1.617.2) and Omicron (B.1.1.529) variants have proven to be of major concern out of all the reported variants, considering their influence on the virus' transmissibility and severity. This study aimed at evaluating the impact of mutations on these two variants on stability and molecular interactions between the viral Spike protein and human angiotensin converting enzyme-2 (hACE-2). The spike proteins receptor binding domain (RBD) was docked with the hACE-2 using HADDOCK servers. To understand and establish the effects of the mutations on the structural stability and flexibility of the RBD-hACE-2 complex, molecular dynamic (MD) simulation of the docked complex was performed and evaluated. The findings from both molecular docking analysis and binding free energy showed that the Omicron (OM) variant has high receptiveness towards hACE-2 versus Delta variant (DT), thereby, responsible for its increase in transmission. The structural stability and flexibility evaluation of variants’ systems showed that mutations on DT and OM variants disturbed the stability of either the spike protein or the RBD-hACE-2 complex, with DT variant having greater instability impact. This study, therefore, assumed this obvious instability observed in DT variant might be associated or responsible for the reported severity in DT variant disease over the OM variant disease. This study provides molecular insight into the effects of OM and DT variants on stability and interactions between SARS-CoV-2 protein and hACE-2. |
| first_indexed | 2024-04-11T10:08:18Z |
| format | Article |
| id | doaj.art-40163a0dd18548079b079240275cf916 |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-11T10:08:18Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-40163a0dd18548079b079240275cf9162022-12-22T04:30:11ZengElsevierInformatics in Medicine Unlocked2352-91482022-01-0133101074A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactionsKehinde A. Idowu0Collins Onyenaka1Omonike A. Olaleye2Corresponding author.; Department of Pharmaceutical and Environmental Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USADepartment of Pharmaceutical and Environmental Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USADepartment of Pharmaceutical and Environmental Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, TX, 77004, USASeveral more infectious SARS-CoV-2 variants have emerged globally since SARS-CoV-2 pandemic and the discovery of the first D614G variant of SARS-CoV-2 spike proteins in 2020. Delta (B.1.617.2) and Omicron (B.1.1.529) variants have proven to be of major concern out of all the reported variants, considering their influence on the virus' transmissibility and severity. This study aimed at evaluating the impact of mutations on these two variants on stability and molecular interactions between the viral Spike protein and human angiotensin converting enzyme-2 (hACE-2). The spike proteins receptor binding domain (RBD) was docked with the hACE-2 using HADDOCK servers. To understand and establish the effects of the mutations on the structural stability and flexibility of the RBD-hACE-2 complex, molecular dynamic (MD) simulation of the docked complex was performed and evaluated. The findings from both molecular docking analysis and binding free energy showed that the Omicron (OM) variant has high receptiveness towards hACE-2 versus Delta variant (DT), thereby, responsible for its increase in transmission. The structural stability and flexibility evaluation of variants’ systems showed that mutations on DT and OM variants disturbed the stability of either the spike protein or the RBD-hACE-2 complex, with DT variant having greater instability impact. This study, therefore, assumed this obvious instability observed in DT variant might be associated or responsible for the reported severity in DT variant disease over the OM variant disease. This study provides molecular insight into the effects of OM and DT variants on stability and interactions between SARS-CoV-2 protein and hACE-2.http://www.sciencedirect.com/science/article/pii/S2352914822002106SARS-CoV-2Variants delta (B.1.617.2)Omicron (B.1.1.529)hACE-2Molecular interaction |
| spellingShingle | Kehinde A. Idowu Collins Onyenaka Omonike A. Olaleye A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions Informatics in Medicine Unlocked SARS-CoV-2 Variants delta (B.1.617.2) Omicron (B.1.1.529) hACE-2 Molecular interaction |
| title | A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions |
| title_full | A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions |
| title_fullStr | A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions |
| title_full_unstemmed | A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions |
| title_short | A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions |
| title_sort | computational evaluation of structural stability of omicron and delta mutations of sars cov 2 spike proteins and human ace 2 interactions |
| topic | SARS-CoV-2 Variants delta (B.1.617.2) Omicron (B.1.1.529) hACE-2 Molecular interaction |
| url | http://www.sciencedirect.com/science/article/pii/S2352914822002106 |
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