An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level

Abstract

Background In the last 2 years, we have been fighting against SARS-CoV-2 viral infection, which continues to claim victims all over the world. The entire scientific community has been mobilized in an attempt to stop and eradicate the infection. A well-known feature of RNA viruses is their high mutational rate, particularly in specific gene regions. The SARS-CoV-2 S protein is also affected by these changes, allowing viruses to adapt and spread more easily. The vaccines developed using mRNA coding protein S undoubtedly contributed to the “fight” against the COVID-19 pandemic even though the presence of new variants in the spike protein could result in protein conformational changes, which could affect vaccine immunogenicity and thus vaccine effectiveness. Results The study presents the findings of an in silico analysis using various bioinformatics tools finding conserved sequences inside SARS-CoV-2 S protein (encoding mRNA) same as in the vaccine RNA sequences that could be targeted by specific host RNA-binding proteins (RBPs). According to the results an interesting scenario emerges involving host RBPs competition and subtraction. The presence of viral RNA in cytoplasm could be a new tool in the virus’s armory, allowing it to improve its chances of survival by altering cell gene expression and thus interfering with host cell processes. In silico analysis was used also to evaluate the presence of similar human miRNA sequences within RBPs motifs that can modulate human RNA expression. Increased cytoplasmic availability of exogenous RNA fragments derived from RNA physiological degradation could potentially mimic the effect of host human miRNAs within the cell, causing modulation of the host cell network. Conclusions Our in silico analysis could aid in shedding light on the potential effects of exogenous RNA (i.e. viruses and vaccines), thereby improving our understanding of the cellular interactions between virus and host biomolecules. Finally, using the computational approach, it is possible to obtain a safety assessment of RNA-based vaccines as well as indications for use in specific clinical conditions.

The Continuous Adaptive Challenge Played by Arboviruses: An <em>In Silico </em>Approach to Define Relevant Molecular Interactions with the Host

“…The suggested analytical pipeline revealed that the mere presence of the "Togaviridae, Flaviviridae, and Bunyaviridae" genomes in the host cell could predict the depletion of particular RBPs and that the depletion of these protein could change metabolic pathways related to the clinical phenotype. Different positive and negative single-strand RNA viruses can sequester RBPs from host proteins to speed up the replication process, disrupts nucleus-cytoplasmic traffic and leads to a spatial redistribution of proteins from the nucleus to the cytoplasm, altering the host cell network [62,63]. It has been demonstrated via individual RBP analysis that dysregulation is related to clinical manifestations such as neuropathy, weakness, and, in severe cases, encephalitis by infecting host neurons.…”

The Continuous Adaptive Challenge Played by Arboviruses: An In Silico Approach to Identify a Possible Interplay between Conserved Viral RNA Sequences and Host RNA Binding Proteins (RBPs)

“…The suggested analytical pipeline revealed that the mere presence of the “ Togaviridae , Flaviviridae , and Bunyavirales ” genomes in the host cell could predict the depletion of particular RBPs and that the depletion of these proteins could change metabolic pathways related to the clinical phenotype. Different positive and negative single-strand RNA viruses can sequester RBPs from host proteins to speed up the replication process, disrupt nucleus-cytoplasmic traffic, and lead to a spatial redistribution of proteins from the nucleus to the cytoplasm, altering the host cell network [ 57 , 58 ]. It has been demonstrated via individual RBP analysis that dysregulation is related to clinical manifestations such as neuropathy, weakness, and, in severe cases, encephalitis by infecting host neurons.…”