Internal drivers of the global pandemic of the Omicron variants of SARS‐CoV‐2

Abstract Background The high transmissibility of the Omicron variants of severe acute respiratory syndrome coronavirus 2 continues to impose a significant burden on public health systems worldwide. Continuous mutations in the virus challenge the efficacy of vaccines and prior immunity from other variants, posing a severe threat to human health. Therefore, there is an urgent need to predict mutations of the Omicron variants and identify key factors influencing their spread. This study investigated critical amino acid mutations of the Omicron variants using epidemiological data and the mechanisms underlying their transmission. The aim was to understand the key factors driving the spread of the Omicron variants and provide insights for effective control and prevention strategies. Methods A total of 488,646 Omicron cases recorded between December 2021 and February 2023 were analyzed using a sliding time window and the Epi Score model, which has high accuracy for the identification of mutation sites. MutPred2, PolyPhen2 and VarSite tools were used to predict future mutations and identify factors driving the prevalence of the Omicron variants. Results Epi Scores showed fluctuating patterns at mutation sites, highlighting N969K, Y505H, N764K, T478K, and S371F mutations on the spike protein as significant for future prevention efforts. The spread of the Omicron variants was linked to changes in the viral entry pathway and improved angiotensin‐converting enzyme 2 (ACE2) binding and immune evasion tactics. Conclusions The findings of this study reveal trends in the evolution of the Omicron variants, including altered cell entry, increased affinity for ACE2, and evasion of the immune system. These factors are critical for understanding the global spread of the Omicron variants and developing effective control strategies.