Structural analysis of Omicron mutated variant in SARS-COV-۲ spike protein

BACKGROUND AND OBJECTIVESSince the beginning of the ۲۱st century, coronaviruses of animal origin have been the cause of several deadly pneumonia epidemics in humans. These include SARS, MERS, and currently, Covid-۱۹, which has spread throughout the world as a pandemic. All viruses, including SARS-CoV-۲, change over time. Although most of the changes do not have much of an effect on the properties of the virus, but some changes may affect their properties. The spread of Omicron (BA.۱), a new type of SARS-CoV-۲, has raised serious concerns due to the large number of mutations in its genome and the lack of knowledge about how these mutations will affect the current SARS-CoV-۲ vaccines and treatments. Investigating the effects of mutations in the RBD (Receptor Binding Domain) and NTD (N-terminal Domain) domains of the spike protein is important for the development of COVID-۱۹ vaccines .MATERIALS AND METHODSIn this study, the structures were modeled using EasyModel, and molecular docking was performed using ClusPro. Computational methods were then used to study the structural effect of mutations in the RBD and NTD regions. Binding affinities were quantitatively calculated using Molecular Dynamics Simulations and free energy calculations.RESULTS AND DISCUSSIONCalculations of the binding free energy using the MM/PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method show that Omicron binds to the ACE۲ (Angiotensin-converting enzyme ۲) receptor with a higher binding energy than the wild type, and also has a higher level of contamination compared to the wild type. Furthermore, the results show that the mutations in the NTD and RBD regions show significant differences from the wild type and can reduce recognition by antibodies, resulting in potential immune evasion and a decrease in the effectiveness of existing vaccines.CONCLUSIONThis study provides a better understanding of the structural changes of the Omicron variant compared to wild type SARS-CoV-۲ for planning new treatments and vaccine candidates against this variant of the virus. Nevertheless, it is mainly limited to structural predictions and these findings require further investigations and experiments in order to be confirmed.

کلیدواژه ها:

Coronavirus ، Omicron variant ، Structural analysis ، Molecular dynamics simulation