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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.
Abstract:
In the frames of a One Health strategy, i.e. a strategy should be able to predict susceptibility to infection in both humans and animals, developing a SARS-CoV-2 mutation tracking system is a goal. We observed that the phylogenetic proximity of vertebrate ACE2 receptors does not affect the binding energy for the viral spike protein. However, all viral variants seem to bind ACE2 better in many animals than in humans. Moreover, two observations highlight that the evolution of the virus started at the beginning of 2020 and culminated with the appearance of the variants. First, codon usage analysis shows that the B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants, similar in the use of codons, are also similar to a virus sampled in January 2020. Second, the host-specific D614G mutation becomes prevalent starting from March 2020. Overall, we show that SARS-CoV-2 undergoes a process of molecular evolution that begins with the optimization of codons followed by the functional optimization of the spike protein.
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