JMIR Publications

ABSTRACT

Background:

The novel coronavirus COVID-19 pandemic caused by SARS-CoV-2 virus currently, in 2020, is the most threatening severe acute respiratory infection in the world with over 40 million people had been infected and more than 0.934 million deaths. It is tempting to speculate that the epidemiological and clinical features may differ among different countries or continents. Genomic comparison of 48,635 SARS-CoV-2 genomes has shown that the average number of mutations per sample was 7.23, and most SARS-CoV-2 strains belong to one of three clades characterized by geographic and genomic specificity: Europe, Asia and North America.

Objective:

The aim of study was to compare the set of SARS-CoV-2 genomes from viruses isolated from the countries in the same meridian (longitude): Italy, Sweden, Congo, but with different climate to reveal similar or different pattern of possible evolutionary pressure signatures in their genomes.

Methods:

We obtained the data from the GISaid repository sampling all the genomes available at that date. Using HyPhy, we achieved the recombination analysis by the GARD method, the trimming, the removal of the stop codons, the phylogenetic tree and the Mixed Effects Model of Evolution analysis. We performed the secondary structures prediction of both sequences (mutated and not) and the “disorder” and “transmembrane” analyses of the protein. We calculated both protein structures with ab initio approach to predict their ontologies and the three-dimensional structures.

Results:

Evolutionary analysis revealed codon 9628 under episodic selective pressure for all four countries, suggesting it as a key site for the virus evolution. Belonging to the P0DTD3 (Y14_SARS2) uncharacterized protein 14, further investigation has been developed showing the codon mutation as responsible for the helical modification in the secondary structure. The codon is placed into the more ordered region of the gene (41-59) and near to the area acting as transmembrane (54-67), suggesting its involvement into the attachment phase of the virus. The predicted structures of P0DTD3 mutated and not, confirmed the importance of the codon to define the protein structure and the ontological analysis of the protein emphasized that the mutation enhances the binding probability.

Conclusions:

Our results shown that codon 9628 is under episodic selective pressure for all four countries. This leads that RNA secondary structure may be affected and consequently the protein product changes T (Threonine) to G (Glycine) in position 50 of the protein. This position is located close to the predicted transmembrane region. The mutation analysis revealed that change from G (Glycine) to D (Aspartic acid) may confer a new function to the protein, binding activity, which in turn may be responsible for attaching the virus to human eukaryotic cells. These can be accessed by in vitro experiments and possibly later facilitate a vaccine design and successful antiviral strategies.