Comparison of the unbinding process of RBD-ACE2 complex between SARS-CoV-2 variants (Delta, delta plus, and Lambda): A steered molecular dynamics simulation

Abstract

ABSTRACT The Delta and Lambda SARS-CoV-2 variants are characterised with the double mutations T478K/L452R, and F490S/L452Q, respectively, in their receptor binding domains (RBDs) of the spike proteins. The Delta Plus variant is one of the Delta variant types with K417N substitution in RBD. Basically, SARS-CoV-2 variants need to bind to Angiotensin-Converting Enzyme 2(ACE2) to enter the host cell. Here, the effects of these mutations were studied on the binding affinity of RBD-ACE2 using steered molecular dynamics (SMD) simulation. According to the results, the rupture force of RBD-ACE2 for the wild type and Delta variant were close to each other, and the minimum and maximum rupture forces occurred in the Delta Plus and Lambda variants, respectively. While T478K and L452R occur adjacent to the RBD binding site and have no major effect on the rupture force of the RBD-ACE2 complex, K417N occurs exactly at the binding site of RBD-ACE2 and causes a decrease in the rupture force for the Delta Plus variant. The results of this study showed that T478K, L452R, and K417N could not justify the infection and transmissibility of the Delta and Delta Plus variants. However, L452Q and F490S were able to affect the binding affinity of the RBD-ACE2 complex.