**1. Introduction**

Variations in the genome and protein expression remain a driver of most diseases with their polygenic phenotypes. Diseases may manifest with time emanating from aberrant protein expression. These biochemical processes are complex in nature, as it involves molecular interactions at both the DNA-RNA/protein level. Within the context of protein-protein interaction (PPI), it has become essential to look at the long-term clinical goal, which could be to identify disease-specific patterns of PPIs, which could serve as a disease- or treatment-responsive biomarkers whose selective measurement may lead to improved diagnosis or prognosis for common human disorders [1].

Interests in the study of variations in DNA/protein have helped to espouse factors germane to influencing biological processes and genome stability. This is more so bearing; genomic integrity is particularly important as they provide the blueprint for the next generation [2]. During cell division, homeostasis is required, and for human health, the genome needs to be copied prudently such that a copy of each chromosome is passed on to the daughter cells. The polygenic nature of some disease phenotypes, controlled by a combination of several genes all playing together makes it essential to unravel biological processes in a piecemeal. For instance, most diseases with a number of persons with inherited predispositions including, heart disease, arteriosclerosis, and some cancers are thought to be polygenic [3].

Looking at these processes within the context of ribonucleic acid (RNA) on the other hand presents different facts. At some point in time, RNA was thought to be much less important than DNA since it did not carry any of the genetic characteristics of an organism. However, lately, it has become obvious that this might not be entirely so bearing, the life cycle of RNA viruses for instance is directed to transport, multiply, and deliver the viral RNA genome into other cells. Fortunately, not all of these viral genomes can encode all proteins in the cell that are required for these known processes to be accomplished. Thus, overcoming this limitation, viruses are known to hijack cellular RNA-binding proteins (RBPs) [4, 5].

Responding to such invasion, host cells do concertedly employ specialized RBPs as a detection mechanism for viral RNAs and their intermediates of replication through the recognition of the molecular signage such as the under-methylated, cap triphosphate ends, and double-stranded RNA (dsRNA) [6]. Beyond this, several other observations have been made [3, 4], highlighting the essential role that RBPs play in regulating the viral life cycle. For instance, it is thought that RBP sensing of viral RNA triggers the cellular antiviral state, which can suppress viral gene expression [6], leading to the inhibition of protein synthesis and the production of interferons [4, 5].

Recently, using multiple proteome-wide approaches [7] had identified RBPs involved in the SARS-CoV-2 life cycle whilst showing that the repertoire of cellular RBPs widely remodels in response to SARS-CoV-2 infection, via proteins involved in antiviral defenses, RNA metabolism, and other pathways.

In all of these processes, transcription factor (TF) mutations have been studied for decades, with RBPs being overlooked as drivers of disease and as therapeutically relevant targets. Now it is established that RBPs determine the fate of transcribed RNAs by regulating their splicing, polyadenylation, translation, subcellular localization, and turnover [8].

For drug repurposing, diseases that are driven by a known or combination of mutants at the protein level are of major attention for direct targeting. Moreover, changes in cellular growth rate and the identity that occur during diseases such as cancer, hemoglobinopathy, etc., are, known to be driven by specific gene expression signatures that are programmed by the activity of DNA-binding TFs and RBP [9]. From recent findings, it is now clear that RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression [9]. Within this context, Liu and Shi [10] earlier established the importance of RBP in Amyotrophic lateral sclerosis (ALS), disease progression. Establishing that the heterogeneous ribonucleoproteins (horn A2/B1) mutation in patients with ALS did not just disable the protein, but instead, the mutation conferred some new toxic properties that scrambled RNA processing, fast-tracking the death of motor neurons [10].

Some other known fact is that missense mutation is a mistake in the DNA and it could arise due to aberrant TF. Missense mutations for instance in tumor suppressors result in its loss of function (LOF) in a variety of manners including loss of stability of the protein or the disruption of a crucial ligand/DNA/protein binding site [11]. The Worldwide Protein Data Bank (wwPDB) have over 88,000 protein

*Recent Progress in Drug Repurposing Using Protein Variants and Amino Acids in Disease… DOI: http://dx.doi.org/10.5772/intechopen.102571*

structures, many of which play vital roles in critical metabolic pathways that may be regarded as potential therapeutic targets and specific databases containing structures of binary complexes [12]. Moreover, a recent breakthrough in molecular science has shown that the key to developing targeted therapy, for diseaseassociated variations is with the critical understanding of the consequences of that variant on the function of the affected protein, and the impact on the pathways in which that protein is involved [9]. Proteins are produced and recycled by some critical processes in their tissue sources and are degraded into necessary amino acids through very controlled bio-signaling and feedback systems. For instance, the salvage pathways are known as a major source of nucleotides for the synthesis of DNA, RNA, and enzyme co-factors.

The disproportion of protein demand, dietary supply, and productions do result in a variety of disease phenotypes due mainly to deficiency, occasioned sometimes by variation properties. A critically important enzyme of purine salvage in rapidly dividing cells for instance is adenosine deaminase (ADA), which catalyzes the deamination of adenosine to inosine. Deficiency in ADA results in the disorder called severe combined immunodeficiency (SCID). This is a genetic disease amongst many others that is characterized by the development of nonfunctional T and B cells due to genetic mutation resulting in heterogeneous clinical phenotype [13].
