Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”?

Abstract

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 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 ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.

SARS-CoV-2 Entry Related Viral and Host Genetic Variations: Implications on COVID-19 Severity, Immune Escape, and Infectivity

“…The pandemic of COVID-19 has caused more than 111 million confirmed cases and more than 2.4 million deaths globally as of 22 February 2021 since the first case was reported from Wuhan, China. The confirmed cases and deaths are rising quickly, and the fast evolution and transmission of SARS-CoV-2 has generated several particular mutations across geographic regions [ 122 , 123 , 124 ]. Since there were no vaccine and treatment-based selective pressures in the early pandemic, the host genetic variability could drive adaptive evolution by selecting for increased genetic diversity in SARS-CoV-2 across geographical regions.…”

Phylogenomics reveals viral sources, transmission, and potential superinfection in early-stage COVID-19 patients in Ontario, Canada

“…However, a global transition from D614 to G614 has occurred since March 1 st with the G614 mutation representing 67% of all sequenced genomes by March 31 and 78% by May 18 observed first in Europe, then North America, then the rest of world 33 . The G614 variant is characteristic of all SARS-CoV-2 genomes in the B.1 and its descendant lineages 36 , and many countries that avoided a first wave of SARS-CoV-2 in January and February 2020 report SARS-CoV-2 genotypes that are almost exclusively the G614 variant 37 . As COVID-19 cases were first introduced in Eastern Ontario from Europe and the USA in mid-late March, it was not unexpected that the G614 mutation comprises 92.6% of cases in this study.…”

Temporal Dynamics and Evolution of SARS-CoV-2 Demonstrate the Necessity of Ongoing Viral Genome Sequencing in Ontario, Canada

“…One of the most prevalent variants observed in SARS-CoV-2 sequenced genomes is the adenine-to-guanine nucleotide substitution at position 23403, a nonsynonymous mutation resulting in an amino acid substitution from aspartic acid to glycine at position 614 in the spike protein. The first D614G mutation was described in a viral genome sequence from China on 24 January 2020 followed by Germany on 28 January 2020 (29). This variant was found in 10% of globally published genomes by 1 March 2020, and became the most dominant form within a month (8).…”