Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2.
Ankita RayTran Thi Minh ThuRita Dos Santos NatividadeRodrigo A MoreiraJoshua D SimpsonDanahe MohammedMelanie KoehlerSimon J L PetitjeanQingrong ZhangFabrice BureauLaurent GilletAdolfo B PomaDavid AlsteensPublished in: ACS nanoscience Au (2024)
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.
Keyphrases
- single molecule
- sars cov
- atomic force microscopy
- angiotensin converting enzyme
- molecular dynamics simulations
- angiotensin ii
- respiratory syndrome coronavirus
- copy number
- living cells
- dna binding
- binding protein
- molecular docking
- high speed
- high resolution
- gene expression
- transcription factor
- mass spectrometry
- data analysis