| Partner: Melanie Koehler |
Recent publications
| 1. | Ray A.♦, Thu Thi Minh T.♦, Santos Natividade Rita d.♦, Azevedo Rodrigo M.♦, Joshua S.♦, Danahe M.♦, Koehler M.♦, Simon P.♦, Qingrong Z.♦, Fabrice B.♦, Laurent G.♦, Poma Bernaola A.M., Alsteens D.♦, Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2, ACS Nanoscience Au, ISSN: 2694-2496, DOI: 10.1021/acsnanoscienceau.3c00060, pp.1-10, 2024 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. Keywords:SARS-Cov-2,Molecular Dynamics ,Immunity,SMFS,Nanomechanics,Free Energy,Jarzynski,Receptor,Protein complex,interfaces Affiliations:
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| 2. | Koehler M.♦, Ray A.♦, Moreira R.A., Juniku B.♦, Poma A.B.♦, Alsteens D.♦, Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/s41467-021-27325-1, Vol.12, pp.6977-1-13, 2021 Abstract: Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity. Keywords:nanomechanics, stability, spike protein, antibody neutralization Affiliations:
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