Effect of Mutations in the SARS-CoV-2 Spike RBD Region of Delta and Delta-Plus Variants on its Interaction with ACE2 Receptor Protein

Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has undergone multiple significant mutations since its detection in 2019 in Wuhan, China. The emergence of new SARS-CoV-2 variants that can spread rapidly and undermine vaccine-induced immunity threatens the end of the COVID-19 pandemic. The delta variant (B.1.617.2) that emerged in India challenges efforts to control the COVID-19 pandemic. In addition to Delta, so-called Delta Plus sub-variants (B.1.617.2.1 and B.1.617.2.2) have become a new cause of global concern. Here we compare the interaction profile of RBD of the spike protein of the Delta and Delta-Plus variant of SARS-CoV-2 with the ACE2 receptor. From the molecular dynamics simulation, we observed the spike protein of Delta and Delta-Plus variant of SARS-CoV-2 utilizes unique strategies to have stable binding with ACE2. Using MM-GBSA/MM-PBSA algorithms, we found the binding affinity of spike protein of the Delta- variant-ACE2 complex is indeed high (GBTOT = -39.36 kcal mol-1, PBTOT= -17.52 kcal mol-1) in comparison with spike protein of Delta-Plus variant-ACE2 Complex (GBTOT = -36.83 kcal mol-1, PBTOT = -16.03 kcal mol-1). Stable binding of spike protein to ACE2 is essential for virus entry, and the interactions between them should be understood well for the treatment modalities.