Mutations in SARS-CoV-2; Consequences in structure, function, and pathogenicity of the virus

Abstract

The third pandemic of coronavirus infection, called COVID-19 disease, began recently in China. The newly discovered coronavirus, entitled SARS-CoV-2, is the seventh member of the human coronaviruses. The main pathogenesis of SARS-CoV-2 infection is severe pneumonia, RNAaemia, accompanied by glass turbidity, and acute cardiac injury. It possesses a single-stranded positive-sense RNA genome which is 60-140 nm in diameter, and has a size of 26-32 kbp. Viral pathogenesis is accomplished with spike glycoprotein through the employment of a membrane-bound aminopeptidase, called the ACE2, as its primary cell receptor. It has been confirmed that various factors such as different national rules for quarantine and various races or genetic backgrounds might influence the mortality and infection rate of COVID-19 in the geographic areas. In addition to various known and unknown factors and host genetic susceptibility, mutations and genetic variabilities of the virus itself have a critical impact on variable clinical features of COVID-19. Although the SARS-CoV-2 genome is more stable than SARS-CoV or MERS-CoV, it has a relatively high dynamic mutation rate with respect to other RNA viruses. It's noteworthy that, some mutations can be founder mutations and show specific geographic patterns. Undoubtedly, these mutations can drive viral genetic variability, and because of genotype-phenotype correlation, resulting in a virus with more/lower/no decrease in natural pathogenic fitness or on the other scenario, facilitating their rapid antigenic shifting to escape the host immunity and also inventing a drug resistance virus, so converting it to a more infectious or deadly virus. Overall, the detection of all mutations in SARS-CoV-2 and their relations with pathological changes is nearly impossible, mostly due to asymptomatic subjects. In this review paper, the reported mutations of the SARS-CoV-2 and related variations in virus structure and pathogenicity in different geographic areas and genotypes are widely investigated. Many studies need to be repeated in other regions/locations for other people to confirm the findings. Such studies could benefit patient-specific therapy, according to genotyping patterns of SARS-CoV-2 distribution.

Keywords: COVID-19; Mutation; Pandemic disease; Pathogenicity; SARS-CoV-2.

Fig. 1

Possible influencing factors on variable symptoms and severity of COVID-19.

Fig. 2

Classification and outbreaks of coronaviruses in human society.

Fig. 3

The genomic organization of SARS-CoV-2. ORF1ab, as the largest gene, encodes the pp1ab protein that contains 15 Nsps (nsp1-nsp10 and nsp12-nsp16). It is located at the 5′ end of the genome. The 3′ terminus of the SARS-CoV-2 genome contains four structural genes, which encode four essential structural proteins: envelope (E), spike protein (S), nucleocapsid protein (N), membrane (M) and a gene for RNA-dependent RNA polymerase.

Fig. 4

Schematic structure of SARS-CoV-2 with the minimal set of structural proteins.

Fig. 5

The mechanism of coronavirus infection and spread. Coronaviruses bind to ACE-2 receptors on the surface of the target cell via their spike proteins. Next, the ACE2 receptor will be cleaved by the TMPRSS2 that results in the activation of the spike protein through which the virus enters the cell.

Fig. 6

Linear positions of the reported mutations in various regions of the SARS-CoV-2 genome.