For example, in 2021, wild-type (WT) SARS-CoV-2 lineages and Gamma variant VOC co-circulated at a low prevalence simultaneously with the then predominant Alpha variant VOC, in Italy as well as elsewhere. However, as more variants emerge and replace prior ones, VOC and VOI classification periodically evolves and updates, with the aim of sharpening surveillance and research targets. All VOCs that have been described so far are characterized by mutations that cause conformational variations in the spike (S) glycoprotein regions that are involved in interactions with host cell surface receptors.
VOCs are defined as variants with an increase in transmissibility or virulence, that are associated with more severe disease, a significant reduction in neutralization by antibodies, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
VOIs are defined as variants with mutations that are associated with a potential increase in transmissibility, disease severity, immune escape, and diagnostic or therapeutic escape. VUM are defined as variants with nucleotide mutations that can be associated with possible increased risk, but with unclear evidence of the epidemiological or phenotypic impact. SARS-CoV-2 variants that are associated with a possible global public health risk are classified as “Variants Under Monitoring” (VUM), “Variants of Interest” (VOI), and “Variants of Concern” (VOC) by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). Over two years of the pandemic, a number of substitutions have been fixed in the viral population, generating new variants or lineages that have been associated with an increase in transmissibility and/or with greater disease severity. Since the first isolate (MN908947.3), that was collected from COVID-19 patients in Hubei province of China in December 2019, SARS-CoV-2 has been evolving at a mutation rate estimated by 1.1 × 10 −3 substitutions per site per year, corresponding to one substitution every 11 days. Finally, we highlighted the role of glycans in the increased RBD flexibility of the monomer in the up conformation of Omicron. Our structural evidence, therefore, is likely involved in the observed different transmissibility of these S mutants. In particular, these last two S regions are known to be involved in the human receptor ACE2 recognition and membrane fusion. However, our studies also revealed structural and dynamic alterations that were concentrated in the aa 627–635 region, on a small region of the receptor binding motif (aa 483–485), and the so-called “fusion-peptide proximal region”. Notwithstanding the great number of mutations that have accumulated, particularly in the Omicron S glycoprotein, our data clearly showed the conservation of some structural and dynamic elements, such as the global motion of the receptor binding domain (RBD). Herein, we carry out an investigation into the dynamic properties of the S glycoprotein, focusing on the much more transmissible Delta and Omicron variants. The vast amount of epidemiologic and genomic data that were gathered as a global response to the COVID-19 pandemic that was caused by SARS-CoV-2 offer a unique opportunity to shed light on the structural evolution of coronaviruses and in particular on the spike (S) glycoprotein, which mediates virus entry into the host cell by binding to the human ACE2 receptor.
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