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.

Jozef Nahalka

doi:10.3389/fgene.2021.763995

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.

Highlights

Life began with the emergence of nucleic and amino acid polymers, before the emergence of more complex proto-cells (Auboeuf, 2020), and the origins of viruses are intertwined with those of ancient proto-cells (Mughal et al, 2020)
The second fact is that the protein–RNA readout can be performed in two directions: N-(AA)n-C versus 5’-(N)n-3’ and C-(AA)n-N versus 5’-(N)n-3’ (Figure 1), so the transcription is done for two amino acid sequences, one for N-(AA)n-C and the second for C(AA)n-N
It is difficult to determine whether the viral proteins or the degradation peptides from the viral proteins recognize and interact with the host-cell RNA in order to post-transcriptionally modify the translation of host-cell proteins; the identified genes are clearly involved in the SARS-CoV-2 life cycle and pathogenesis

Summary

Introduction

Life began with the emergence of nucleic and amino acid polymers, before the emergence of more complex proto-cells (Auboeuf, 2020), and the origins of viruses are intertwined with those of ancient proto-cells (Mughal et al, 2020). In the early prebiotic stage, there was likely a stereochemical era during the evolution of the genetic code, with direct interactions between nucleotides and amino acids (Yarus et al, 2009; Yarus, 2017). It seems that glycine, alanine, aspartic acid, and valine (G, A, D, and V, respectively), which are coded with GNC codons, were the first amino acids in the first peptides/proteins (Ikehara, 2009, 2016). The principle of the protein–RNA recognition code is explained in Figure 1 and is depicted on the crystal structure of the ribosomal release factor 1 (RF1), which interacts with the P-site tRNA (3D5A). The CCA76 readout is performed by CC and CA readout-2-letter code (2-L), or by the C plus C plus A readout-1-letter code (1-L), as was proposed previously (Nahalka, 2014, 2019)

Methods

Results

Discussion

Conclusion