Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV‑2 Variants with ACE2

• Published in: ACS Nanoscience Au Vol. 4; no. 2; pp. 136 - 145
• Main Authors: Ray, Ankita, Minh Tran, Thu Thi, Santos Natividade, Rita dos, Moreira, Rodrigo A., Simpson, Joshua D., Mohammed, Danahe, Koehler, Melanie, L Petitjean, Simon J., Zhang, Qingrong, Bureau, Fabrice, Gillet, Laurent, Poma, Adolfo B., Alsteens, David
• Format: Journal Article Web Resource
• Language: English
• Published: United States American Chemical Society 17.04.2024; American Chemical Society (ACS)
• Subjects: 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; 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
• ISSN: 2694-2496; 2694-2496
• DOI: 10.1021/acsnanoscienceau.3c00060

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.