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Microbes & Immunity SARS-CoV-2 complementary classification

1. Introduction During the initial phase of the COVID-19 pandemic,
the relatively low number of infections limited the
Severe acute respiratory syndrome coronavirus 2 opportunities for genetic diversification within the SARS-
(SARS-CoV-2) is a member of the family Coronaviridae CoV-2 genome. With fewer viral replication cycles, the
that was first characterized in early 2020. This virus is the accumulation of mutations was constrained, resulting in a
1-3
causative agent of coronavirus disease 2019 (COVID-19) 37
and long COVID. COVID-19 has been recognized as the lower frequency of SARS-CoV-2 variant emergence. At
4,5
pandemic of the 21 century. It ranges in manifestations from this stage, mutations in the spike (S) protein, particularly
6
st
asymptomatic infections and mild cold-like illnesses to more within the receptor-binding domain (RBD), which
severe forms that result in significant morbidity and mortality, mediates interaction with the human angiotensin-
especially in elderly patients with chronic illnesses. 7-11 converting enzyme-2 (ACE2) receptor, were rarely
observed. As transmission increased globally, the virus
37
Like other members of Coronaviridae, SARS-CoV-2 evolved, with a positive selection of certain substitutions
has a genome comprising a positive-sense, single- that conferred higher transmissibility (e.g., D614G). 38,39
stranded RNA with a linear configuration. 12,13 Despite the Over time, specific S protein substitutions that enhanced
lack of accurate characterization of the exact origins of SARS-CoV-2’s ability to bind more efficiently to human
SARS-CoV-2, the early spread of the virus has been well cells became more prevalent and led to the emergence of
documented. 14-18 Phylogenetic analyses of SARS-CoV-2 genetic variants with epidemiological advantages. Notably,
sequences from the early infections in China suggested the Alpha (B.1.1.7) variant, first identified in the UK, and
that the first human cases likely occurred in late 2019. 19,20 the Delta (B.1.617.2) variant, which originated in India,
The present evidence suggests that the emergence of both demonstrated significantly higher transmission rates
SARS-CoV-2 resulted from recombination events than earlier circulating strains. 40-42 These variants carried
between bat SARS-like coronaviruses and, possibly, key S protein mutations, such as N501Y in the Alpha
coronaviruses found in pangolins, leading to cross-species variant and L452R and P681R in the Delta variant, which
transmission. 21-24 More recent research suggested that enhanced their ability to infect host cells and possibly
direct spillover from bats remains the most likely scenario, contributed to their global dominance at different phases
with limited genomic evidence supporting a significant during the pandemic. 43,44 The progressive emergence of
role of pangolins in the emergence of SARS-CoV-2. 25,26
more transmissible variants indicates the role of natural
The earliest available SARS-CoV-2 genomes were selection in shaping SARS-CoV-2 evolution, favoring
obtained from patients in December 2019. These mutations that increase infectivity while the virus continues
27
early viral sequences provided key insights into the to adapt to human hosts. 45
genetic structure and early divergence of SARS-CoV-2.
3
Chinese researchers conducted phylogenetic analyses At present, SARS-CoV-2 variants are designated
comparing these genomes with known bat and pangolin as distinct viral lineages when they exhibit genetic
coronaviruses to infer the likely ancestral form of the changes deemed significant enough to warrant separate
virus. Based on mutational differences, they identified classification, as determined by the WHO Coronavirus
28
an ancestral genome type, designated “S”, and a more Network (CoViNet). 35,46 Since the onset of the COVID-19
dominant derived type, labeled “L”, to reflect specific pandemic, the continuous evolution of SARS-CoV-2 has
amino acid substitutions. Concurrently, Western led to the identification of multiple VOCs and variants
29
researchers conducted independent analyses using similar of interest (VOIs). 43,47,48 These designations have been
methodologies but assigned different nomenclatures to based on the projected capacity of emerging variants
describe the early divergence of SARS-CoV-2. Instead of to outcompete previously circulating strains through
“S” and “L,” they labeled the ancestral strain as “A” and the increased transmissibility or the necessity to adjust public
derived strain as “B”. 30-33 Over time, the B lineage continued health interventions. 49-51 This classification system has been
to mutate, giving rise to sub-lineages, including B.1, which important to facilitate epidemiological surveillance and
became the predominant SARS-CoV-2 lineage globally. risk assessment. However, its primary reliance on limited
34
This lineage eventually diversified into major global genetic divergence and evolving phenotypic criteria, rather
variants of concern (VOCs), which the World Health than on consistent, functionally meaningful differentiation,
Organization (WHO) formally labeled as Alpha, Beta, highlights the opportunity for refining the system.
Gamma, Delta, and Omicron variants. The early genomic Incorporating genetic and evolutionary benchmarks could
35
studies illustrated the complex evolutionary dynamics of enhance the alignment between nomenclature and the
SARS-CoV-2, highlighting both early genetic bottlenecks underlying virological or clinical significance of emerging
and the subsequent rapid adaptation of the virus. 36 SARS-CoV-2 variants. 52-54

Volume 2 Issue 3 (2025) 88 doi: 10.36922/MI025190042