Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the “confined virus”?

Abstract

The Coronavirus disease 19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome.Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2.These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely.

Do the Moroccan SARS-CoV-2 genetic diversity hamper the use of the developed universal vaccines in Morocco?

“…Compared to the reference sequence of Wuhan-Hu-1/2019, strains from North Africa harbored 4 to 15 genetic variants, of which 1 to 11 are involved in the change of amino acids. These results are consistent with the mutation rate previously reported in SASR-CoV-2 from different geographic areas (13,(23)(24)(25).…”

“…Focusing on SARS-CoV-2 Moroccan strains, four mutations were common within all strains, which is in agrrement with recent studies showing a low frequency of recurrent mutations in thousands of SARS-CoV-2 genomes (13,23).…”

“…The Q57H mutation was taken away end of February in Africa (Senegal), Europe (France and Belgium) and North America (USA and Canada). Likewise, our previous study (13) showed that D614G had no impact on the two-dimensional or three-dimensional structure of advanced glycoprotein. Of the other three non-synonymous mutations that are variable between the strains from the four countries, T265I mutation (in nsp2) was identified Moroccan, Tunisian and Algerian strains, while K2798R (in nsp4transmembrane domain-2) and T5020I mutations (in nsp12-RdRp) were observed within the strains from Tunisia-Egypt and Tunisia-Morocco, respectively.…”

“…Of the other three non-synonymous mutations that are variable between the strains from the four countries, T265I mutation (in nsp2) was identified Moroccan, Tunisian and Algerian strains, while K2798R (in nsp4transmembrane domain-2) and T5020I mutations (in nsp12-RdRp) were observed within the strains from Tunisia-Egypt and Tunisia-Morocco, respectively. Among these five mutations, four (D614G, Q57H, T265I and T5020I) have been considered as hotspot mutations in a large population (13,23).…”

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges

“…35 It is worthy of note that the sequences of 30,983 complete genomes from 80 countries situated in Africa, Asia, America, and Oceania, were analyzed by Alouane et al . 36 In comparison to the reference genome Wuhan-Hu-1 genome, the analysis revealed the occurrence of 3,206 variant sites with uniform distribution in all genome sequences analyzed . 36 A low frequency of mutations of about 182 mutations, with a prevalence of 5.67% was reportedly observed .…”