Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein
The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5464 |
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| author | Stefano Borocci Carmen Cerchia Alessandro Grottesi Nico Sanna Ingrid Guarnetti Prandi Nabil Abid Andrea R. Beccari Giovanni Chillemi Carmine Talarico |
| author_facet | Stefano Borocci Carmen Cerchia Alessandro Grottesi Nico Sanna Ingrid Guarnetti Prandi Nabil Abid Andrea R. Beccari Giovanni Chillemi Carmine Talarico |
| author_sort | Stefano Borocci |
| collection | DOAJ |
| description | The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein. Herein, we employed microsecond-long molecular dynamics simulations to study the impact of the mutations of the S glycoprotein in SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7), termed the “UK variant”, in comparison with the wild type, with the aim to decipher the structural basis of the reported increased infectivity and virulence. The simulations provided insights on the different dynamics of UK and wild-type S glycoprotein, regarding in particular the Receptor Binding Domain (RBD). In addition, we investigated the role of glycans in modulating the conformational transitions of the RBD. The overall results showed that the UK mutant experiences higher flexibility in the RBD with respect to wild type; this behavior might be correlated with the increased transmission reported for this variant. Our work also adds useful structural information on antigenic “hotspots” and epitopes targeted by neutralizing antibodies. |
| first_indexed | 2024-03-10T11:09:47Z |
| format | Article |
| id | doaj.art-e0f0d859250b42d985401dcbf9675ed3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:09:47Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e0f0d859250b42d985401dcbf9675ed32023-11-21T20:54:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211546410.3390/ijms22115464Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike GlycoproteinStefano Borocci0Carmen Cerchia1Alessandro Grottesi2Nico Sanna3Ingrid Guarnetti Prandi4Nabil Abid5Andrea R. Beccari6Giovanni Chillemi7Carmine Talarico8Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyDepartment of Pharmacy, University of Napoli “Federico II”, Via D. Montesano 49, 80131 Napoli, ItalyDepartment HPC, CINECA, Via dei Tizii 6, 00185 Roma, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 3, 56124 Pisa, ItalyLaboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy, University of Monastir, Rue Ibn Sina, Monastir 5000, TunisiaDompé Farmaceutici SpA, Via Campo di Pile, 67100 L’Aquila, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyDompé Farmaceutici SpA, Via Campo di Pile, 67100 L’Aquila, ItalyThe COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein. Herein, we employed microsecond-long molecular dynamics simulations to study the impact of the mutations of the S glycoprotein in SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7), termed the “UK variant”, in comparison with the wild type, with the aim to decipher the structural basis of the reported increased infectivity and virulence. The simulations provided insights on the different dynamics of UK and wild-type S glycoprotein, regarding in particular the Receptor Binding Domain (RBD). In addition, we investigated the role of glycans in modulating the conformational transitions of the RBD. The overall results showed that the UK mutant experiences higher flexibility in the RBD with respect to wild type; this behavior might be correlated with the increased transmission reported for this variant. Our work also adds useful structural information on antigenic “hotspots” and epitopes targeted by neutralizing antibodies.https://www.mdpi.com/1422-0067/22/11/5464SARS-CoV-2COVID-19spikevariantsmolecular dynamics |
| spellingShingle | Stefano Borocci Carmen Cerchia Alessandro Grottesi Nico Sanna Ingrid Guarnetti Prandi Nabil Abid Andrea R. Beccari Giovanni Chillemi Carmine Talarico Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein International Journal of Molecular Sciences SARS-CoV-2 COVID-19 spike variants molecular dynamics |
| title | Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein |
| title_full | Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein |
| title_fullStr | Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein |
| title_full_unstemmed | Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein |
| title_short | Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein |
| title_sort | altered local interactions and long range communications in uk variant b 1 1 7 spike glycoprotein |
| topic | SARS-CoV-2 COVID-19 spike variants molecular dynamics |
| url | https://www.mdpi.com/1422-0067/22/11/5464 |
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