Mutational hotspot in the SARS-CoV-2 Spike protein N-terminal domain conferring immune escape potential

amplicon-based SARS-CoV-2 genotyping,

Our team at SOPHiA GENETICS continues to work to help advance the efforts of SARS-CoV-2 surveillance and research. During the first stages of the pandemic, we leveraged our experience in NGS and developed a robust solution for full-genome analysis of SARS-CoV-2 to identify circulating and emerging strains. Recently, our genomic experts have worked with international partners to offer new guidelines in amplicon-based SARS-CoV-2 genotyping, overall improving data quality and confidence.

Going beyond the detection and surveillance of emerging strains, including the B.1.1.7 “UK variant” or the B.1.167.2 “Indian variant”, the SOPHiA DDM™ platform enables the analyses of individual mutations.

As we continue to advance the analyses of SARS-CoV-2, our research experts have identified an important and novel mutational hotspot.

Our researchers recently reported a striking increase in the frequency of recruitment of diverse substitutions at a critical residue, W152, positioned in the N-terminal domain (NTD) of the Spike protein. The NTD is the most rapidly mutating part of the Spike protein, and these substitutions at position W152 have been observed repeatedly across independent phylogenetic and geographical contexts.

W152 is an important interaction point for neutralizing antibodies, and these frequent mutation recruitment events were reported with a clear increase in intensity since the end of 2020 (week 55 of the pandemic). Notably, researchers have reported this specific mutation has spurred >150 clusters that directly or indirectly contributed to contaminating over 15,000 patients.

As vaccination efforts improve around the globe, this research SOPHiA DDM™ platform enables continues to be fundamental to better understand the variants that “escape” immunity.

Read the preprint available now.