Emergence of adaptive mutations of the spike In SARS-CoV-2

Abstract

Surveillance of mutants of SARS-CoV-2 aims to monitor the appearance of new variants that could potentially change the biological properties of the virus. During the first year of SARS-CoV-2 evolution, different variants have been detected with different degrees of biological impact on the virus and also on the epidemic. We have detected two mutations of the spike protein of SARS-CoV-2 that have appeared independently multiple times in different genetic backgrounds and hosts, possibly indicating they could increase viral fitness. Interestingly, when both mutations appeared together, the genotype increased in frequency more than the individual mutants. This variant that we call Variant of Interest 1 and includes 12 other single nucleotide polymorphisms but no deletions with respect to the reference genome. VOI.1 appeared after the First epidemic Wave in Spain, and subsequently migrated and increased in frequency in 8 countries. VOI.1 includes a cluster of sequences that have acquired the concerning mutation E484K, which could result in antibody escape. We explored if these two mutations confer a greater capacity to the virus to produce more particles. Unexpectedly, we find a reduction in infectivity of this variant versus the 20EU1 in two different cell lines. However, clinical results differ slightly and we found that individuals infected with VOI.1 have similar levels of viral RNA in nasopharyngeal swabs than patients infected with 20EU1 variants, both of them significantly higher than non 20EU1 lineages. Finally, in order to assess the risk of VOI.1 because of antibody escape, we explored the impact on immunogenicity. A moderate but significant reduction in sensitivity to neutralization by sera from convalescent donors obtained from the early period of the pandemic was observed. Overall we could detect and monitor the spread of a variant of interest which could pose a potential risk. The expansion of such variants has allowed the acquisition of another potentially risky mutation, present in other variants of concern, which could pose an additional threat.