PT - JOURNAL ARTICLE AU - Tarun Mishra AU - Rishikesh Dalavi AU - Garima Joshi AU - Atul Kumar AU - Pankaj Pandey AU - Sanjeev Shukla AU - Ram K Mishra AU - Ajit Chande TI - SARS-CoV-2 spike E156G/Δ157-158 mutations contribute to increased infectivity and immune escape AID - 10.26508/lsa.202201415 DP - 2022 Jul 01 TA - Life Science Alliance PG - e202201415 VI - 5 IP - 7 4099 - https://www.life-science-alliance.org/content/5/7/e202201415.short 4100 - https://www.life-science-alliance.org/content/5/7/e202201415.full SO - Life Sci. Alliance2022 Jul 01; 5 AB - Breakthrough infections by emerging SARS-CoV-2 variants raise significant concerns. Here, we sequence-characterized the spike gene from breakthrough infections that corresponded to B.1.617 sublineage. Delineating the functional impact of spike mutations revealed that N-terminal domain (NTD)-specific E156G/Δ157-158 contributed to increased infectivity and reduced sensitivity to vaccine-induced antibodies. A six-nucleotide deletion (467–472) in the spike-coding region introduced this change in the NTD. We confirmed the presence of E156G/Δ157-158 from cases concurrently screened, in addition to other circulating spike (S1) mutations such as T19R, T95I, L452R, E484Q, and D614G. Notably, E156G/Δ157-158 was present in more than 90% of the sequences reported from the USA and UK in October 2021. The spike-pseudotyped viruses bearing a combination of E156G/Δ157-158 and L452R exhibited higher infectivity and reduced sensitivity to neutralization. Notwithstanding, the post-recovery plasma robustly neutralized viral particles bearing the mutant spike. When the spike harbored E156G/Δ157-158 along with L452R and E484Q, increased cell-to-cell fusion was also observed, suggesting a combinatorial effect of these mutations. Our study underscores the importance of non-RBD changes in determining infectivity and immune escape.