Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex
<p dir="ltr">Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly...
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| مؤلفون آخرون: | , |
| منشور في: |
2022
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| _version_ | 1864513519107440640 |
|---|---|
| author | Wesam S. Ahmed (10170053) |
| author2 | Angelin M. Philip (13138647) Kabir H. Biswas (5705864) |
| author2_role | author author |
| author_facet | Wesam S. Ahmed (10170053) Angelin M. Philip (13138647) Kabir H. Biswas (5705864) |
| author_role | author |
| dc.creator.none.fl_str_mv | Wesam S. Ahmed (10170053) Angelin M. Philip (13138647) Kabir H. Biswas (5705864) |
| dc.date.none.fl_str_mv | 2022-07-22T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fmolb.2022.846996 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Decreased_Interfacial_Dynamics_Caused_by_the_N501Y_Mutation_in_the_SARS-CoV-2_S1_Spike_ACE2_Complex/25624299 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Microbiology ACE2 COVID-19 molecular dynamics simulation SARS-CoV-2 S1 spike protein N501Y mutant |
| dc.title.none.fl_str_mv | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha, beta, and gamma variants (B.1.1.7, B.1.351, and P.1 lineages, respectively) are of great significance in that they contain several mutations that increase their transmission rates as evident from clinical reports. By the end of March 2021, these variants were accounting for about two-thirds of SARS-CoV-2 variants circulating worldwide. Specifically, the N501Y mutation in the S1 spike receptor binding domain (S1-RBD) of these variants have been reported to increase its affinity for ACE2, although the basis for this is not entirely clear yet. Here, we dissect the mechanism underlying the increased binding affinity of the N501Y mutant for ACE2 using molecular dynamics (MD) simulations of the available ACE2-S1-RBD complex structure (6M0J) and show a prolonged and stable interfacial interaction of the N501Y mutant S1-RBD with ACE2 compared to the wild type S1-RBD. Additionally, we find that the N501Y mutant S1-RBD displays altered dynamics that likely aids in its enhanced interaction with ACE2. By elucidating a mechanistic basis for the increased affinity of the N501Y mutant S1-RBD for ACE2, we believe that the results presented here will aid in developing therapeutic strategies against SARS-CoV-2 including designing of therapeutic agents targeting the ACE2-S1-RBD interaction.</p><p dir="ltr">Corrigendum: Decreased interfacial dynamics caused by the N501Y mutation in the SARS-CoV-2 S1 spike:ACE2 complex: Frontiers in Molecular Biosciences: <a href="https://dx.doi.org/10.3389/fmolb.2022.1018464" rel="noreferrer" target="_blank">https://dx.doi.org/10.3389/fmolb.2022.1018464</a>, published online 19 October 2022.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Molecular Biosciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fmolb.2022.846996" target="_blank">https://dx.doi.org/10.3389/fmolb.2022.846996</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b7453a8324cd91620ba208f71dc97cef |
| identifier_str_mv | 10.3389/fmolb.2022.846996 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25624299 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 ComplexWesam S. Ahmed (10170053)Angelin M. Philip (13138647)Kabir H. Biswas (5705864)Biological sciencesBiochemistry and cell biologyGeneticsMicrobiologyACE2COVID-19molecular dynamics simulationSARS-CoV-2S1 spike proteinN501Y mutant<p dir="ltr">Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha, beta, and gamma variants (B.1.1.7, B.1.351, and P.1 lineages, respectively) are of great significance in that they contain several mutations that increase their transmission rates as evident from clinical reports. By the end of March 2021, these variants were accounting for about two-thirds of SARS-CoV-2 variants circulating worldwide. Specifically, the N501Y mutation in the S1 spike receptor binding domain (S1-RBD) of these variants have been reported to increase its affinity for ACE2, although the basis for this is not entirely clear yet. Here, we dissect the mechanism underlying the increased binding affinity of the N501Y mutant for ACE2 using molecular dynamics (MD) simulations of the available ACE2-S1-RBD complex structure (6M0J) and show a prolonged and stable interfacial interaction of the N501Y mutant S1-RBD with ACE2 compared to the wild type S1-RBD. Additionally, we find that the N501Y mutant S1-RBD displays altered dynamics that likely aids in its enhanced interaction with ACE2. By elucidating a mechanistic basis for the increased affinity of the N501Y mutant S1-RBD for ACE2, we believe that the results presented here will aid in developing therapeutic strategies against SARS-CoV-2 including designing of therapeutic agents targeting the ACE2-S1-RBD interaction.</p><p dir="ltr">Corrigendum: Decreased interfacial dynamics caused by the N501Y mutation in the SARS-CoV-2 S1 spike:ACE2 complex: Frontiers in Molecular Biosciences: <a href="https://dx.doi.org/10.3389/fmolb.2022.1018464" rel="noreferrer" target="_blank">https://dx.doi.org/10.3389/fmolb.2022.1018464</a>, published online 19 October 2022.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Molecular Biosciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fmolb.2022.846996" target="_blank">https://dx.doi.org/10.3389/fmolb.2022.846996</a></p>2022-07-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fmolb.2022.846996https://figshare.com/articles/journal_contribution/Decreased_Interfacial_Dynamics_Caused_by_the_N501Y_Mutation_in_the_SARS-CoV-2_S1_Spike_ACE2_Complex/25624299CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256242992022-07-22T03:00:00Z |
| spellingShingle | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex Wesam S. Ahmed (10170053) Biological sciences Biochemistry and cell biology Genetics Microbiology ACE2 COVID-19 molecular dynamics simulation SARS-CoV-2 S1 spike protein N501Y mutant |
| status_str | publishedVersion |
| title | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| title_full | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| title_fullStr | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| title_full_unstemmed | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| title_short | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| title_sort | Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex |
| topic | Biological sciences Biochemistry and cell biology Genetics Microbiology ACE2 COVID-19 molecular dynamics simulation SARS-CoV-2 S1 spike protein N501Y mutant |