Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference
Abstract To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-18507-y |
| _version_ | 1818082435714252800 |
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| author | Vedat Durmaz Katharina Köchl Andreas Krassnigg Lena Parigger Michael Hetmann Amit Singh Daniel Nutz Alexander Korsunsky Ursula Kahler Centina König Lee Chang Marius Krebs Riccardo Bassetto Tea Pavkov-Keller Verena Resch Karl Gruber Georg Steinkellner Christian C. Gruber |
| author_facet | Vedat Durmaz Katharina Köchl Andreas Krassnigg Lena Parigger Michael Hetmann Amit Singh Daniel Nutz Alexander Korsunsky Ursula Kahler Centina König Lee Chang Marius Krebs Riccardo Bassetto Tea Pavkov-Keller Verena Resch Karl Gruber Georg Steinkellner Christian C. Gruber |
| author_sort | Vedat Durmaz |
| collection | DOAJ |
| description | Abstract To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring. |
| first_indexed | 2024-12-10T19:22:04Z |
| format | Article |
| id | doaj.art-599fc97a10244ebfa110d685b1388078 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T19:22:04Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-599fc97a10244ebfa110d685b13880782022-12-22T01:36:28ZengNature PortfolioScientific Reports2045-23222022-08-0112111310.1038/s41598-022-18507-yStructural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type referenceVedat Durmaz0Katharina Köchl1Andreas Krassnigg2Lena Parigger3Michael Hetmann4Amit Singh5Daniel Nutz6Alexander Korsunsky7Ursula Kahler8Centina König9Lee Chang10Marius Krebs11Riccardo Bassetto12Tea Pavkov-Keller13Verena Resch14Karl Gruber15Georg Steinkellner16Christian C. Gruber17Innophore GmbHInnophore GmbHInnophore GmbHInnophore GmbHInstitute of Molecular Biosciences, University of GrazInnophore GmbHInnophore GmbHInnophore GmbHInnophore GmbHInnophore GmbHAWS Diagnostic Development Initiative-Global Social ImpactAmazon Web Services EMEA SARLAmazon Web Services EMEA SARLInstitute of Molecular Biosciences, University of GrazInnophore GmbHInstitute of Molecular Biosciences, University of GrazInnophore GmbHInnophore GmbHAbstract To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring.https://doi.org/10.1038/s41598-022-18507-y |
| spellingShingle | Vedat Durmaz Katharina Köchl Andreas Krassnigg Lena Parigger Michael Hetmann Amit Singh Daniel Nutz Alexander Korsunsky Ursula Kahler Centina König Lee Chang Marius Krebs Riccardo Bassetto Tea Pavkov-Keller Verena Resch Karl Gruber Georg Steinkellner Christian C. Gruber Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference Scientific Reports |
| title | Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference |
| title_full | Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference |
| title_fullStr | Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference |
| title_full_unstemmed | Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference |
| title_short | Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference |
| title_sort | structural bioinformatics analysis of sars cov 2 variants reveals higher hace2 receptor binding affinity for omicron b 1 1 529 spike rbd compared to wild type reference |
| url | https://doi.org/10.1038/s41598-022-18507-y |
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