Preliminary Structural Data Revealed That the SARS-CoV-2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity

Abbas Khan., Dong Qing Wei, Kafila Kousar, Jehad Abubaker, Sajjad Ahmad, Javaid Ali, Fahd Al-Mulla, Syed Shujait Ali, N. Nizam-Uddin, Abrar Mohammad Sayaf, Anwar Mohammad

Research output: Contribution to journalArticlepeer-review

Abstract

The evolution of new SARS-CoV-2 variants around the globe has made the COVID-19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor-binding motif (RBM) of the receptor-binding domain (RBD) spike glycoprotein, i. e. L452R-E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R-E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic-stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural-dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS-CoV-2 variants.

Original languageEnglish
JournalChemBioChem
Early online date23 Jun 2021
DOIs
Publication statusE-pub ahead of print - 23 Jun 2021

Keywords

  • ACE2-spike docking
  • B.1.617 variant
  • biophysical simulation
  • dissociation constant
  • SARS-CoV-2

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