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. Here, the authors combine single-molecule atomic force spectroscopy measurements and molecular dynamics simulations to investigate the binding of spike proteins from four SARS-CoV-2 variants of concern (VoC) to the human ACE2 receptor. They observe an increase in the RBD-ACE2 complex stability for several of the VoCs and derive how the mutations affect the kinetic, thermodynamic and structural properties of complex formation.
【저자키워드】 Proteins, Atomic force microscopy, Nanoscale biophysics, Computational biophysics, 【초록키워드】 SARS-CoV-2, pathology, Mutation, Immunity, knowledge, SARS-CoV-2 variant, Spike protein, Molecular dynamics simulation, stability, N501Y, viral replication, Microscopy, N501Y mutation, molecular, virulence, Antibody neutralization, binding, kinetic, significant increase, complex, human ACE2 receptor, while, viral mutation, Affect, isolate, RBD-ACE2, observé, greater, affected, significantly, investigated, unlikely, provide, atomic, increase in, structural property, thermodynamic, cellular detail, several variant, 【제목키워드】 neutralization, SARS-CoV-2 variant, Receptor binding,