Abstract
Emerging SARS-CoV-2 variants raise concerns about our ability to withstand the Covid-19 pandemic, and therefore, understanding mechanistic differences of those variants is crucial. In this study, we investigate disparities between the SARS-CoV-2 wild type and five variants that emerged in late 2020, focusing on the structure and dynamics of the spike protein interface with the human angiotensin-converting enzyme 2 (ACE2) receptor, by using crystallographic structures and extended analysis of microsecond molecular dynamics simulations. Dihedral angle principal component analysis (PCA) showed the strong similarities in the spike receptor binding domain (RBD) dynamics of the Alpha, Beta, Gamma, and Delta variants, in contrast with those of WT and Epsilon. Dynamical perturbation networks and contact PCA identified the peculiar interface dynamics of the Delta variant, which cannot be directly imputable to its specific L452R and T478K mutations since those residues are not in direct contact with the human ACE2 receptor. Our outcome shows that in the Delta variant the L452R and T478K mutations act synergistically on neighboring residues to provoke drastic changes in the spike/ACE2 interface; thus a singular mechanism of action eventually explains why it dominated over preceding variants.
【초록키워드】 ACE2, pandemic, Mutation, COVID-19 pandemic, variant, SARS-CoV-2 variant, Delta, molecular dynamics, outcome, delta variant, variants, principal component analysis, Spike protein, Receptor binding domain, L452R, RBD, Epsilon, Gamma, Alpha, Beta, receptor, molecular, mechanism of action, wild type, Delta variants, Analysis, angiotensin, PCA, Contact, similarity, can not, contact with, direct contact, Principal component, singular, T478K, Spike receptor binding domain, residue, human Angiotensin-converting enzyme, human ACE2 receptor, crystallographic structure, FIVE, Dihedral angle, raise, changes in, the spike protein, explain, drastic, provoke, the SARS-CoV-2, 【제목키워드】 Dynamics, Delta, interface, Perturbation, the SARS-CoV-2,