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Updated: Oct 11, 2025

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
Codon usage, phylogeny and binding energy estimation predict the evolution of SARS-CoV-2.
Matteo Calcagnile1, Tiziano Verri1, Maurizio Salvatore Tredici1
1Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, 73100 Lecce, Italy.
This study reveals SARS-CoV-2 evolution, showing viral variants bind animal ACE2 receptors better than human ones. This highlights the need for a mutation tracking system for One Health strategies.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- A One Health strategy requires predicting SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection susceptibility in both humans and animals.
- Developing a robust SARS-CoV-2 mutation tracking system is crucial for this strategy.
Purpose of the Study:
- To investigate the molecular evolution of SARS-CoV-2.
- To analyze the binding affinity of viral variants to vertebrate ACE2 receptors.
- To understand the timeline and drivers of SARS-CoV-2 evolution.
Main Methods:
- Phylogenetic analysis of ACE2 receptors.
- Binding energy calculations for viral spike protein-ACE2 interactions.
- Codon usage analysis of viral variants.
- Tracking the prevalence of the D614G mutation over time.
Main Results:
- Phylogenetic proximity of vertebrate ACE2 receptors does not influence binding energy with the viral spike protein.
- Viral variants exhibit enhanced binding to animal ACE2 receptors compared to human ACE2.
- Codon usage patterns indicate SARS-CoV-2 evolution began in early 2020, with variants like Alpha, Beta, and Delta sharing similarities with a January 2020 sample.
- The host-specific D614G mutation became prevalent starting March 2020.
Conclusions:
- SARS-CoV-2 undergoes molecular evolution, initially optimizing codon usage and subsequently enhancing spike protein function.
- Viral evolution favors better binding to animal ACE2 receptors, with implications for interspecies transmission.
- Understanding these evolutionary dynamics is key for developing effective One Health surveillance and control strategies.
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