Structural impact of a new spike Y170W mutation detected in early emerging SARS-CoV-2 Omicron variants in France

Abstract

To assess the genetic characteristics of the early emerging SARS-CoV-2 Omicron variant strains, we retrospectively analyzed a collection of 150 nasopharyngeal samples taken from a series of outpatient cases tested positive by a referenced qRT-PCR assay during the reported period of Omicron variant emergence in December 2021, in northeastern region of France. Next Generation Sequencing (NGS) analysis of SARS-CoV-2 spike sequences revealed that only 3 (2 %) of these detected strains were Omicron variants, while 147 (98 %) were identified as previously described delta variants. Our phylogenetic analyzes of SARS-CoV-2 RNA genomes showed that these French early emerging Omicron variants may have originated from South Africa or India. In addition, whole viral genome sequences NGS comparison analyzes allowed us to identify an original and uncharacterized Y170W spike mutation that was weakly and transiently detected during the period of SARS-CoV-2 Omicron variant emergence in human populations. Molecular modeling and docking experiments indicated that this original mutated residue Y170W was neither directly involved in binding to the SARS-CoV-2 receptor ACE2 nor in interacting with known neutralizing antibody sites. However, this new mutation may be responsible for preventing the transition from the closed to the open Spike conformation, thus promoting the early emergence of the Omicron variant. Overall, these results underscore the epidemiological utility of a routine whole-genome viral NGS strategy that enables genotypic characterization of emerging or mutant SARS-CoV-2 variants, which could have significant implications for public health policy.

Keywords: COVID-19; Epidemiology; NGS; Omicron variant; SARS-CoV-2; Spike gene.