Exploring the intrinsic dynamics of SARS-CoV-2, SARS-CoV and MERS-CoV spike glycoprotein through normal mode analysis using anisotropic network model

COVID-19 caused by SARS-CoV-2 have become a global pandemic with serious rate of fatalities. SARSCoV and MERS-CoV have also caused serious outbreak previously but the intensity was much lower than the ongoing SARS-CoV-2. The main infectivity factor of all the three viruses is the spike glycoprotein. In this study we have examined the intrinsic dynamics of the prefusion, lying state of trimeric S protein of these viruses through Normal Mode Analysis using Anisotropic Network Model. The dynamic modes of the S proteins of the aforementioned viruses were compared by root mean square inner product (RMSIP), spectral overlap and cosine correlation matrix. S proteins show homogenous correlated or anticorrelated motions among their domains but direction of C-a atom among the spike proteins show less similarity. SARS-CoV-2 spike shows high vertically upward motion of the receptor binding motif implying its propensity for binding with the receptor even in the lying state. MERS-CoV spike shows unique dynamical motion compared to the other two S protein indicated by low RMSIP, spectral overlap and cosine correlation value. This study will guide in developing common potential inhibitor molecules against closed state of spike protein of these viruses to prevent conformational switching from lying to standing state. (c) 2020 Elsevier Inc. All rights reserved.

Automated summary

COVID-19 caused by SARS-CoV-2 has become a serious global pandemic, with a higher intensity compared to previous outbreaks caused by SARS-CoV and MERS-CoV. The study reveals that S proteins of these viruses share similar dynamic patterns but show differences in the directionality of the spike proteins.