Perceptions into causes and consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants. Issue 1 (27th February 2023)

• Record Type: Journal Article
• Authors: Laxminarayana, Dama
• Is Part Of: Rheumatology & autoimmunity. Volume 3:Issue 1(2023)
• Page Start: 1
• Page End: 8
• Publication Date: 2023-02-27
• Subjects: gene regulation -- innate immunity -- mutations -- RNA editing enzymes -- SARS‐CoV‐2 pathogenesis -- type I interferons; Rheumatology; Rheumatism -- Research; Autoimmunity; Periodicals; 616.723
• DOI: 10.1002/rai2.12065
• Languages: English
• ISSNs: 2767-1410

Abstract

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants are emerging worldwide and pathogenicity varies widely from no symptoms to death. The SARS‐CoV‐2 is evolving as lineages like Alpha, Beta, Gamma, Epsilon, Iota, Delta, and Omicron in the course of time. The main reasons for such viral evolution are (a) the imperfect nature of SARS‐CoV‐2 RNA polymerase, and viral exonuclease mediated proofreading functions resulting in the generation of mutations in viral genomes; (b) fusions of the 5′ leader sequence to unexpected 3′ sites, and transcription regulatory sequences (TRSs) in subgenomic RNAs (sgRNAs), which result in the generation of structural variants and novel open reading frames; (c) these viruses are combated by the host type I interferons (IFNs). In such a process IFNs upregulate viral RNA editing APOBEC3G/F and ADAR1 genes, which induce mutations in viral genomes. These factors play important roles in causing viral evolution and the emergence of more efficient SARS‐CoV‐2 genomes, which escape the host immune defense system, and vaccine‐elicited antibodies and impede therapeutic strategies. The main challenges we now face are how to control future SARS‐CoV‐2 evolution, the elimination of their deleterious side effects, and the onset of new diseases as aftermaths of SARS‐CoV‐2 infections. Preventive measures like (a) the development of broadly neutralizing antibodies and novel vaccines, therapies based on genomics and proteomics data will help in avoiding, and/or minimizing SARS‐CoV‐2 infections; (b) targeted therapies, application of patient‐based precision medicine methodology can help in achieving the goal and avoiding unwanted deleterious side effects and the onset of SARS‐CoV‐2 infections mediated several diseases in future. Abstract : Graphical description of molecular mechanisms involved in the induction of mutations in severe acute respiratory syndrome coronavirus 2 genomes in the host cellular milieu, which are responsible for the emergence of variants. Highlights: The molecular mechanisms involved in viral evolution are enlightened. Such information will help to better understand the root causes for the emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, their pathophysiology, and the mechanism(s) of infection. Precision medicine‐based strategies may help to eliminate and/or minimize the onset of future aftermaths of SARS‐CoV‐2 infections and their deleterious effects. Ultimately, such efforts may pave the way for developing better vaccines and therapeutic regimens to control and/or prevent SARS‐CoV‐2 infections as well as the onset of associated autoimmune and other diseases in susceptible individuals.