Insights into the structure and dynamics of SARS-CoV-2 spike glycoprotein double mutant L452R-E484Q.

ABSTRACT

The Receptor Binding Domain (RBD) of SARS-CoV-2, located on the S1 subunit, plays a vital role in the virus binding and its entry into the host cell through angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, understanding the dynamic effects of mutants on the SARS-CoV-2 RBD is essential for discovering drugs to inhibit the virus binding and disrupt its entry into the host cells. A recent study reported a double mutant of SARS-CoV-2, L452R-E484Q, located in the RBD region. Thus, this study employed various computational algorithms and methods to understand the structural impact of both individual variants L452R, E484Q, and the double mutant L452R-E484Q on the native RBD of spike glycoprotein. The effects of the mutations on native RBD structure were predicted by in silico algorithms, which predicted changes in the protein structure and function upon the mutations. Subsequently, molecular dynamics (MD) simulations were employed to understand the conformational stability and functional changes on the RBD upon the mutations. The comparative results of MD simulation parameters displayed that the double mutant induces significant conformational changes in the spike glycoprotein RBD, which may alter its biological functions. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03151-0.