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The Diverse Nature of the Molecular Interactions That Govern the COV-2 Variants' Cell Receptor Affinity Ranking and

Fredy Sussman1, Daniel S Villaverde1

  • 1Department of Organic Chemistry, Faculty of Chemistry, Universidad de Santiago de Compostela, 15784 Santiago de Compostela, Spain.

International Journal of Molecular Sciences
|March 13, 2024
PubMed

Insights

Computational analysis reveals distinct binding mechanisms for Delta and Omicron variants to host cells. Delta shows higher binding affinity, while Omicron

Area of Science:

  • Virology
  • Structural Biology
  • Computational Biology

Background:

  • Viral infectivity and virulence are determined by spike protein interactions with host receptors.
  • Understanding mutations in variants of concern (VOCs) is crucial for predicting virulence and guiding therapeutic strategies.

Purpose of the Study:

  • To computationally assess the binding affinity of spike proteins from Wild Type, Delta, and Omicron variants to the ACE2 receptor.
  • To elucidate the molecular mechanisms underlying spike-receptor interactions for different VOCs.

Main Methods:

  • Application of a suite of computational protocols with increasing complexity.
  • Calculation of spike binding affinity to the ACE2 cell receptor for three VOCs.

Main Results:

  • Delta and Omicron variants exhibit different molecular mechanisms for spike attachment to the ACE2 receptor.
  • All computational protocols predict higher receptor-binding affinity for the Delta variant compared to Wild Type and Omicron.
  • Omicron variant displays significant variability in spike binding affinity, linked to its spike-receptor complex's structural plasticity.

Conclusions:

  • The structural plasticity of the Omicron spike-receptor complex may explain variability in in vitro binding results.
  • This plasticity could contribute to the Omicron variant's comparatively lower virulence than earlier strains.
  • Further hypotheses are proposed to explain Omicron's reduced virulence.
Keywords:
COV-2molecular mechanics calculationsmolecular mechanismspike–receptor affinitiesvariant infectivityvariants of concern

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