Temporal analysis and comparative genomic study of SARS-CoV-2 variants across Uttar Pradesh, India: Insights from the first and second COVID-19 waves

Abstract

The rapid emergence of genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after late 2020, lead to origin of the term “variant of concern” and became the prime issue for the health of the human populations across the globe. Genome surveillance provides the information about the functional consequences of the variants and their divergence. Presently, we report and compare the nucleotide sequences of the isolated SARS-CoV-2 genomes at two different time-frame i.e. first wave (June- September, 2020) and second wave (April-May, 2021) from Lucknow, Uttar Pradesh, India. We employed the Oxford Nanopore MINION system and ARTIC protocol for sequencing, achieving >90x genome coverage in approximately 90% of samples. Increased mutation density in viral spike proteins were the cause of higher transmission and infectivity of second wave. The second wave exhibited a higher mutation density in viral spike proteins, likely contributing to increased transmission and infectivity. Notable spike mutations included receptor-binding domain (RBD) mutations (L452R, T478K, D614G), N-terminal domain (NTD) mutations (T17R, G142D, Δ156–157, A222V), and furin cleavage site (FCS) mutations (P681R, D950N). The functional consequences of common and unique variants among the first and second wave were evaluated by Sorting Intolerant from Tolerant (SIFT) and Protein Variant Effect Analyser (PROVEAN). Furthermore, we extensively investigated phylogenetic clustering of the genome sequences by Nextstrain and identified the contrasting divergence between first and second wave. Different sub division of delta clade (21I, 21 A, 21 J) and 21 B (kappa) with mutations primarily in spike proteins and nucleocapsid proteins, were exclusive to the second wave. Our study identified changes in spike proteins and nucleocapsid potentially contributing to increased transmission and infectivity during the second wave. Loci specific variant map for different countries across the world suggested the appearance of large number of variants associated with ORF1a during the second wave in India. Overall, the data underscores the dynamic nature of viral evolution during different phases of an outbreak, highlighting the importance of continuous genomic surveillance to track and understand viral mutations and their implications for public health interventions.