The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor
The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/5/497 |
| _version_ | 1797569289738256384 |
|---|---|
| author | Esther S. Brielle Dina Schneidman-Duhovny Michal Linial |
| author_facet | Esther S. Brielle Dina Schneidman-Duhovny Michal Linial |
| author_sort | Esther S. Brielle |
| collection | DOAJ |
| description | The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue–residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV–ACE2 complex. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies. |
| first_indexed | 2024-03-10T20:08:49Z |
| format | Article |
| id | doaj.art-cbca5c9cef194d53899641b7cb9da9aa |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:08:49Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-cbca5c9cef194d53899641b7cb9da9aa2023-11-19T23:05:51ZengMDPI AGViruses1999-49152020-04-0112549710.3390/v12050497The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human ReceptorEsther S. Brielle0Dina Schneidman-Duhovny1Michal Linial2Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelDepartment of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelDepartment of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, IsraelThe COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue–residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV–ACE2 complex. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies.https://www.mdpi.com/1999-4915/12/5/497molecular dynamicsvirus–host interactionsprotein–protein complexcoronavirus evolutionACE2SARS-CoV-2 |
| spellingShingle | Esther S. Brielle Dina Schneidman-Duhovny Michal Linial The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor Viruses molecular dynamics virus–host interactions protein–protein complex coronavirus evolution ACE2 SARS-CoV-2 |
| title | The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor |
| title_full | The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor |
| title_fullStr | The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor |
| title_full_unstemmed | The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor |
| title_short | The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor |
| title_sort | sars cov 2 exerts a distinctive strategy for interacting with the ace2 human receptor |
| topic | molecular dynamics virus–host interactions protein–protein complex coronavirus evolution ACE2 SARS-CoV-2 |
| url | https://www.mdpi.com/1999-4915/12/5/497 |
| work_keys_str_mv | AT esthersbrielle thesarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor AT dinaschneidmanduhovny thesarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor AT michallinial thesarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor AT esthersbrielle sarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor AT dinaschneidmanduhovny sarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor AT michallinial sarscov2exertsadistinctivestrategyforinteractingwiththeace2humanreceptor |