Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants.
Melanie KoehlerAnkita RayRodrigo A MoreiraBlinera JunikuAdolfo B PomaDavid AlsteensPublished in: Nature communications (2021)
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.
Keyphrases
- sars cov
- molecular dynamics
- atomic force microscopy
- respiratory syndrome coronavirus
- copy number
- healthcare
- single molecule
- angiotensin ii
- escherichia coli
- angiotensin converting enzyme
- density functional theory
- staphylococcus aureus
- binding protein
- drug induced
- molecular dynamics simulations
- high glucose
- biofilm formation
- cystic fibrosis
- mass spectrometry
- candida albicans