Codon usage, phylogeny and binding energy estimation predict the evolution of SARS-CoV-2

Matteo Calcagnile; Tiziano Verri; Maurizio Salvatore Tredici; Patricia Forgez; Marco Alifano; Pietro Alifano

doi:10.1016/j.onehlt.2021.100352

Codon usage, phylogeny and binding energy estimation predict the evolution of SARS-CoV-2

One Health. 2021 Dec:13:100352. doi: 10.1016/j.onehlt.2021.100352. Epub 2021 Nov 24.

Authors

Matteo Calcagnile¹, Tiziano Verri¹, Maurizio Salvatore Tredici¹, Patricia Forgez², Marco Alifano^{3

4}, Pietro Alifano¹

Affiliations

¹ Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, 73100 Lecce, Italy.
² INSERM UMR-S 1124 T3S, Eq 5 Cellular Homeostasis, Cancer and Therapy, University of Paris, Campus Saint Germain, Paris, France.
³ Thoracic Surgery Department, Cochin Hospital, APHP Centre, University of Paris, France.
⁴ INSERM U1138 Team «Cancer, Immune Control, and Escape», Cordeliers Research Center, University of Paris, France.

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.

Keywords: ACE2; ACE2 phylogeny; Animal host; B.1.1.7 (alpha) SARS-CoV-2 variant B.1.351 (Beta) SARS-CoV-2 variant; B.1.617.2 (delta) SARS-CoV-2 variant; Codon usage; Docking; Molecular evolution; SARS-CoV-2.