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The massive increase in COVID-19 infection had generated a second wave in India during May–June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain. [Display omitted] • Comparative genomics of two emerging SARS-CoV-2 variants (B.1.1.7 and B. 1.617.2). • Evolutionary epidemiology, geographical distribution and country-wise transmission patterns of study of Alpha.1.1.7 and Delta. 1.617.2. • Landscape of significant mutations such as L452R, E484Q, N501Y, D614G and P681R. • RBD-hACE2 receptor binding pattern analysis in B.1.1.7 and B. 1.617.2 compare to Wuhan reference strain. [ABSTRACT FROM AUTHOR]