3.1. Emergence of SARS-CoV-2 variants and Spike mutations
Since the first emergence of SARS-CoV-2 in 2019 [1], the virus spread globally with minimal mutations in the spike protein until the end of 2020. From late 2020, Alpha, Beta and Gamma variants dominated over the wild type SARS-CoV-2. By the mid and late 2021, Delta and Omicron subtypes dominated Alpha, Beta and Gamma variants as shown in figure 1A and B. Until November 2021, the Delta variant was considered highly transmissible and pathogenic. In contrast, by the end of 2021, a new variant (Omicron) with high mutations emerged in South Africa [18] with increased transmis-sibility and modest pathogenicity (Figure 1A and B). The number of SARS-CoV-2 cases rapidly increased after the emergence of the Omicron variant which gradually trans-mitted across different countries within a short time span.
The random accumulation of mutations gradually increased in different lineages of SARS-CoV-2 variants due to the rapid transmission and disease severity (Figure 2 A and B). The variants reported early (Alpha, Beta, Gamma and Delta) had minimal spike mutations (8-12 aa). However, the recent Omicron variant shows the highest (>30 aa) mutations across the spike protein (Figure 2A and B). These variants might have co-evolved with host adaptation and selective immune pressure, raising the chances of having antibody escape variants [7,12,13].