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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 #MMPMID35723340
Nahalka J
Curr Issues Mol Biol 2022[Feb]; 44 (2): 791-816 PMID35723340show ga
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(H)alphabeta cells. In the viral cycle, E supports the COPII-SCAP-SREBP-HSP90alpha 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 alpha/beta-mediated transport to the nucleus, which explains the positive effect of ivermectin, a blocker of importins alpha/beta. 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.