Theoretical Analysis of S, M and N Structural Proteins by the Protein–RNA Recognition Code Leads to Genes/proteins that Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis

Abstract

In this conceptual review, based on the protein–RNA recognition code, some theoretical sequences were detected in the spike (S), membrane (M) and capsid (N) proteins that may post-transcriptionally regulate the host genes/proteins in immune homeostasis, pulmonary epithelial tissue homeostasis, and lipid homeostasis. According to the review of literature, the spectrum of identified genes/proteins shows that the virus promotes IL1α/β–IL1R1 signaling (type 1 immunity) and immunity defense against helminths and venoms (type 2 immunity). In the alteration of homeostasis in the pulmonary epithelial tissue, the virus blocks the function of cilia and the molecular programs that are involved in wound healing (EMT and MET). Additionally, the protein–RNA recognition method described here identifies compatible sequences in the S1A-domain for the post-transcriptional promotion of PIKFYVE, which is one of the critical factors for SARS-CoV-2 entry to the host cell, and for the post-transcriptional repression of xylulokinase XYLB. A decrease in XYLB product (Xu5P) in plasma was proposed as one of the potential metabolomics biomarkers of COVID-19. In summary, the protein–RNA recognition code leads to protein genes relevant to the SARS-CoV-2 life cycle and pathogenesis.

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

“…Decreased plasma product from XYLB was hypothesized as one of the potential metabolomics biomarkers of COVID-19. [34][35][36] CLDN6 (Claudin-6) has a large role in tight junction-specific obliteration of the intercellular space (which has a role in microbial infection), and also functions as a receptor for hepatitis C virus entry into hepatic cells. UBTF gene is associated with neurodegeneration, brain atrophy, intellectual disability, retinoblastoma, pediatric acute myeloblastic leukemia.…”

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

“…For example, PLA2 contributes to anti-helminth defense by hydrolyzing membrane phospholipids (Th2-defence, production of IL4 and IL5 cytokines, allergy/asthma) [181]. Previous "1-L transcription" revealed that SARS-CoV-2 reorients the immune response to type 2 immunity [10]. On the other hand, PLA2 products represent the first step in the cyclooxygenase (COX) pathway.…”

“…This bioinformatics study focuses on possible post-transcriptional regulation of the SARS-CoV-2 spike protein S1 subunit in host cells/tissues. Ten regulated genes were previously identified by 1-L transcription [10] in relation to protein-RNA post-transcriptional regulation of the S1 subunit: PARG (poly[ADP-ribose] glycohydrolase), DAW1 (dynein assembly factor with WD repeats 1), ZYG11B (zyg-11 family member B, cell cycle regulator), PIKFYVE (phosphoinositide kinase, FYVE-type zinc finger containing), RABEP1 (rabaptin, RAB GTPase binding effector protein 1), MSRA (methionine sulfoxide reductase A), PLB1 (phospholipase B1), TJP2 (tight-junction protein 2), ZEB2 (zinc finger E-box binding homeobox 2), and XYLB (xylulokinase B). As confirmed experimentally by others, these genes/proteins are important during SARS-CoV-2 infection.…”

1-L Transcription in Alzheimer’s Disease

“…1-L transcription is a simple computational method successfully tested on the life cycle and pathogenesis of SARS-CoV-2 [ 11 , 12 ]. In this method, the amino acid sequence of the RNA binding protein (RBP) was transcribed with a 1-L protein-RNA recognition code into compatible RNA sequences, which were then used for classical BLASTn screening in the human transcriptome to identify genes that can be post-transcriptionally regulated by the analyzed RBP.…”