A Comprehensive Account of SARS-CoV-2 Genome structure, Incurred mutations, Lineages and COVID-19 Vaccination Program

Abstract

This review collates information on the onset of COVID-19, SARS-CoV-2 genome architecture, emergence of novel viral lineages that drove multiple waves of infection around the world and standard and fast track development of vaccines. With the passage of time, the continuously evolving SARS-CoV-2 has acquired an expanded mutational landscape. The functional characterization of spike protein mutations, the primary target of diagnostics, therapeutics and vaccines has revealed increased transmission, pathogenesis and immune escape potential in the variant lineages of the virus. The incurred mutations have also resulted in substantial viral neutralization escape to vaccines, monoclonal, polyclonal and convalescent antibodies presently in use. The present situation suggests the need for development of precise next-generation vaccines and therapeutics by targeting the more conservative genomic viral regions for providing adequate protection.

Durability of the Neutralizing Antibody Response to mRNA Booster Vaccination Against SARS-CoV-2 BA.2.12.1 and BA.4/5 Variants

“…Over the course of the pandemic, SARS-CoV-2 has evolved to become more transmissible and less sensitive to humoral immunity, resulting in several major SARS-CoV-2 variants of concerns. Mutations such as K417N and E484K/A, present in the Beta, Gamma, and Omicron variants, have led to increased resistance to neutralizing antibodies (nAbs) (Ghimire et al, 2022; Rajpal et al, 2022). The Omicron variant in particular has exhibited the most substantial immune evasion due to the alarming number of amino acid mutations in its spike gene, totaling more than 30, with 16 concentrated in the receptor binding domain (RBD) (O’Toole et al, 2021).…”

Innovative translational platforms for rapid developing clinical vaccines against COVID‐19 and other infectious disease

“…For introduction of the viral vectored vaccines, there is no more understandable description than the vivid citation of exemplifying the covid‐19 vaccines caused by SARS‐CoV2, which is perhaps rather familiar to most people at present. [ 29 ] SARS‐CoV2 is a positive‐sense single‐stranded RNA‐enveloped virus with only one genome, which consists of approximately 30,000 bp in length encoding around 9860 amino acids and corresponding to 14 functional open reading frames (ORFs). [ 30 ] These ORFs contain two noncoding regions at both ends, and multiple regions that encode for 29 proteins, including 16 nonstructural proteins (NSPs), 9 accessory proteins, and 4 structural proteins.…”

“…1) Attachment and entry of SAR2‐ CoV‐2 requires priming by transmembrane serine protease 2 (TMPRSS2) which cleaves the S protein into S1 and S2 portions, facilitating 2) S1 targeting and binding of the receptor angiotensin‐Converting Enzyme 2 (ACE2), followed by receptor‐mediated endocytosis of the virion into the host cell (A permitted citation from Ref. [29] and Ref. [31]).…”

The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline

“…The coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has continuously evolved and mutated into a range of variants with differing transmission and pathogenesis characteristics [ 1 ]. One approach to help understand acute and long-term sequelae associated with SARS-CoV-2 infection, particularly the neurological consequences [ 2 ], is to investigate the complex binding interactions of the SARS-CoV-2 virus with various receptors in the human body.…”