Codon Usage and Context Analysis of Genes Modulated during SARS-CoV-2 Infection and Dental Inflammation

Abstract

The overexpression of SARS-CoV-2 primary receptors and co-receptors (ACE2, TMPRSS2, FURIN, and CD147) enhance the likeliness of SARS-CoV-2 infection. The genes for same receptors are overexpressed in the periodontal tissues of periodontitis patients. On the other hand, BMAL1 is recognized to play a crucial role in regulating pulmonary inflammation and enhancing susceptibility to viral infection. Silenced BMAL1 disrupts circadian transcriptional regulations, enhances vulnerability to SARS-CoV-2 infections, and may trigger the further production of TNF-α and other pro-inflammatory cytokines that propagate the cytokine storm and exacerbate periodontal inflammation. Therefore ACE2, TMPRSS2, FURIN, CD147, and BMAL1 are the crossroads between SARS-CoV-2 and Periodontitis genes. The enhanced expression of ACE2, TMPRSS2, FURIN, and CD147 and the diminished expression of BMAL1 may be a strategy to check both ailments simultaneously. In gene manipulation techniques, oligos are introduced, which contain all the necessary information to manipulate gene expression. The data are derived from the studies on genes' molecular patterns, including nucleotide composition, dinucleotide patterns, relative synonymous codon usage, codon usage bias, codon context, and rare and abundant codons. Such information may be used to manipulate the overexpression and underexpression of the genes at the time of SARS-CoV-2 infection and periodontitis to mitigate both ailments simultaneously; it can be explored to uncover possible future treatments.

Keywords: ACE2; BMAL1; CD147; FURIN; SARS-CoV-2; TMPRSS2; codon context; dental; periodontitis; rare codons.

Figure 1

Average per cent composition of the genes.

Figure 2

Contour plot for the dinucleotide odds ratio. The blue color shows underrepresentation, while the red shows an overrepresentation of dinucleotides.

Figure 3

Heat map analysis for RSCU values of A/T and G/C ending codons of ACE2, CD147, FURIN, TMPRSS2, and BMAL1. Analysis revealed the dominance of G/C ending codons in CD147, FURIN, and TMPRSS2 genes while the dominance of A/T ending codons in ACE2 and BMAL1.

Figure 4

Rare codons in (A) Six-fold, (B) four-fold, (C) two-fold, and (D) three-fold degenerate codons in ACE2, BMAL1, TMPRSS2, FURIN, and CD147 genes. Codons less than 10 in number in a standard transcript of 1000 bp (normalized transcript length) were considered rare. Codons that are altogether absent in the transcript of a gene are boxed with red color.

Figure 4

Rare codons in (A) Six-fold, (B) four-fold, (C) two-fold, and (D) three-fold degenerate codons in ACE2, BMAL1, TMPRSS2, FURIN, and CD147 genes. Codons less than 10 in number in a standard transcript of 1000 bp (normalized transcript length) were considered rare. Codons that are altogether absent in the transcript of a gene are boxed with red color.

Figure 5

Codon context analysis for (A) ACE2, (B) BMAL1, (C) CD147, (D) FURIN, and (E) TMPRSS2 genes. The green color shows the preferred codon pair, while the red color represents the rejected codon pairs. Statistically insignificant values are expressed as black. The grey color indicates unrepresented codon pairs.

Figure 5

Codon context analysis for (A) ACE2, (B) BMAL1, (C) CD147, (D) FURIN, and (E) TMPRSS2 genes. The green color shows the preferred codon pair, while the red color represents the rejected codon pairs. Statistically insignificant values are expressed as black. The grey color indicates unrepresented codon pairs.

Figure 5

Codon context analysis for (A) ACE2, (B) BMAL1, (C) CD147, (D) FURIN, and (E) TMPRSS2 genes. The green color shows the preferred codon pair, while the red color represents the rejected codon pairs. Statistically insignificant values are expressed as black. The grey color indicates unrepresented codon pairs.