Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis

Abstract

The theoretical protein-RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes showed that the virus post-transcriptionally promotes or represses the genes involved in the SARS-CoV-2 life cycle. The identified genes/proteins are also involved in adaptive immunity, in the function of the cilia and wound healing (EMT and MET) in the pulmonary epithelial tissue, in Alzheimer's and Parkinson's disease and in type 2 diabetes. For example, the E-protein promotes BHLHE40, which switches off the IL-10 inflammatory "brake" and inhibits antiviral T_Hαβ cells. In the viral cycle, E supports the COPII-SCAP-SREBP-HSP90α transport complex by the lowering of cholesterol in the ER and by the repression of insulin signaling, which explains the positive effect of HSP90 inhibitors in COVID-19 (geldanamycin), and E also supports importin α/β-mediated transport to the nucleus, which explains the positive effect of ivermectin, a blocker of importins α/β. In summary, transcription of the envelope protein by the 1-L protein-RNA recognition code leads to genes/proteins that are relevant to the SARS-CoV-2 life cycle and pathogenesis.

Keywords: COVID-19; SARS-CoV-2; bioinformatics method; envelope protein; identified genes; protein–RNA recognition.

Figure 1

The principle of the proposed protein–RNA recognition code [9] is depicted in the interactions between the 5′AAUAAA hexamer and CPSF30 and WDR33 [11]. One-letter code—second nucleotide in the codons; two-letter code—first two nucleotides in the codons. Amino acids are in capitals, and nucleotides are in small letters. The compatibility to adenine is in blue, and the compatibility to uridine is in red. The PAS hexamer, poly(A) signal, is organized into three pairs (a1–a2, a4–a5 and u3–a6). In WDR33, the nucleotide sequence readout is performed by the KRMRK, NKVK and ETILQ sequences (2-L) and by the QQQAMQQ sequence (1-L). To read the 5′AAUAAA signal by 1-L, humans and plants use a “c” spacer (A or P), but Drosophila and Saccharomyces do not.

Figure 2

The SARS-CoV-2 envelope protein and the identified genes by 1-L transcription. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed), and yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted). Alignments are compatible with the transmembrane domain (TMD); they can be divided into those compatible with the N-terminus of the TMD (highlighted in cyan), compatible with the C-terminus of the TMD (highlighted in magenta) and compatible with both ends of the TMD (highlighted in gray).

Figure 3

The graphic illustration of “Altered immune homeostasis as a consequence of SARS-CoV-2 infection”. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed); yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted).

Figure 4

The graphical illustration of “Altered homeostasis in the pulmonary epithelial tissue during the SARS-CoV-2 infection”. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed); yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted).

Figure 5

The graphical illustration of “Altered neuronal homeostasis as a consequence of SARS-CoV-2 infection”. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed); yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted).

Figure 6

The graphical illustration of “SARS-CoV-2 infection alters glucose homeostasis to T2D”. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed); yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted).

Figure 7

The graphical illustration/scheme of “The host genes/proteins involved in the life cycle of SARS-CoV-2”. Green highlights show the alignments with the complement sequence (post-transcriptionally repressed); yellow highlights show the alignments with the reverse complement sequence (post-transcriptionally promoted).