Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV‑2 Variants with ACE2
The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force...
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Published in | ACS Nanoscience Au Vol. 4; no. 2; pp. 136 - 145 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article Web Resource |
Language | English |
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American Chemical Society
17.04.2024
American Chemical Society (ACS) |
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Abstract | The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies. |
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AbstractList | The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies. |
Author | Bureau, Fabrice Ray, Ankita Santos Natividade, Rita dos Koehler, Melanie Zhang, Qingrong Poma, Adolfo B. Gillet, Laurent Moreira, Rodrigo A. L Petitjean, Simon J. Alsteens, David Mohammed, Danahe Simpson, Joshua D. Minh Tran, Thu Thi |
AuthorAffiliation | Faculty of Materials Science and Technology Immunology-Vaccinology Lab of the Faculty of Veterinary Medicine Liège University Basque Center for Applied Mathematics WELBIO department Vietnam National University Louvain Institute of Biomolecular Science and Technology WEL Research Institute University of ScienceVNU HCM Laboratory of Cellular and Molecular Immunology, GIGA Institute |
AuthorAffiliation_xml | – name: WEL Research Institute – name: Liège University – name: Faculty of Materials Science and Technology – name: Vietnam National University – name: WELBIO department – name: Louvain Institute of Biomolecular Science and Technology – name: Immunology-Vaccinology Lab of the Faculty of Veterinary Medicine – name: University of ScienceVNU HCM – name: Basque Center for Applied Mathematics – name: Laboratory of Cellular and Molecular Immunology, GIGA Institute |
Author_xml | – sequence: 1 givenname: Ankita orcidid: 0000-0002-5059-9598 surname: Ray fullname: Ray, Ankita organization: Louvain Institute of Biomolecular Science and Technology – sequence: 2 givenname: Thu Thi orcidid: 0000-0001-8357-8462 surname: Minh Tran fullname: Minh Tran, Thu Thi organization: Vietnam National University – sequence: 3 givenname: Rita dos orcidid: 0000-0002-0123-4760 surname: Santos Natividade fullname: Santos Natividade, Rita dos organization: Louvain Institute of Biomolecular Science and Technology – sequence: 4 givenname: Rodrigo A. surname: Moreira fullname: Moreira, Rodrigo A. organization: Basque Center for Applied Mathematics – sequence: 5 givenname: Joshua D. orcidid: 0000-0002-8823-8130 surname: Simpson fullname: Simpson, Joshua D. organization: Louvain Institute of Biomolecular Science and Technology – sequence: 6 givenname: Danahe surname: Mohammed fullname: Mohammed, Danahe organization: Louvain Institute of Biomolecular Science and Technology – sequence: 7 givenname: Melanie surname: Koehler fullname: Koehler, Melanie organization: Louvain Institute of Biomolecular Science and Technology – sequence: 8 givenname: Simon J. surname: L Petitjean fullname: L Petitjean, Simon J. organization: Louvain Institute of Biomolecular Science and Technology – sequence: 9 givenname: Qingrong surname: Zhang fullname: Zhang, Qingrong organization: Louvain Institute of Biomolecular Science and Technology – sequence: 10 givenname: Fabrice surname: Bureau fullname: Bureau, Fabrice organization: Liège University – sequence: 11 givenname: Laurent surname: Gillet fullname: Gillet, Laurent organization: Liège University – sequence: 12 givenname: Adolfo B. orcidid: 0000-0002-8875-3220 surname: Poma fullname: Poma, Adolfo B. email: apoma@ippt.pan.pl – sequence: 13 givenname: David orcidid: 0000-0001-9229-113X surname: Alsteens fullname: Alsteens, David email: david.alsteens@uclouvain.be organization: WEL Research Institute |
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Keywords | ACE2 Atomic force microscopy SARS-CoV-2 RBD biolayer interferometry Steered molecular dynamics convalescent patient sera SARS-CoV-2 ACE2 RBD Atomic force microscopy Steered molecular dynamics biolayer interferometry convalescent patient sera |
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SubjectTerms | ACE2 Atomic force microscopy Biochemistry, Molecular Biology biolayer interferometry Biomechanics Biophysics Biotechnology Chemical Sciences Chemistry (miscellaneous) Computer Science convalescent patient sera Human health sciences Immunologie & maladie infectieuse Immunology & infectious disease Life Sciences Materials Science (miscellaneous) Mechanics Modeling and Simulation Physics RBD SARS-CoV-2 Sciences de la santé humaine Steered molecular dynamics |
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Title | Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV‑2 Variants with ACE2 |
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