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  1. Article: Changes within the P681 residue of spike dictate cell fusion and syncytia formation of Delta and Omicron variants of SARS-CoV-2 with no effects on neutralization or infectivity.

    Kuzmina, Alona / Korovin, Dina / Cohen Lass, Ido / Atari, Nofar / Ottolenghi, Aner / Hu, Pan / Mandelboim, Michal / Rosental, Benyamin / Rosenberg, Elli / Diaz-Griffero, Felipe / Taube, Ran

    Heliyon

    2023  Volume 9, Issue 6, Page(s) e16750

    Abstract: The rapid spread and dominance of the Omicron SARS-CoV-2 lineages have posed severe health challenges worldwide. While extensive research on the role of the Receptor Binding Domain (RBD) in promoting viral infectivity and vaccine sensitivity has been ... ...

    Abstract The rapid spread and dominance of the Omicron SARS-CoV-2 lineages have posed severe health challenges worldwide. While extensive research on the role of the Receptor Binding Domain (RBD) in promoting viral infectivity and vaccine sensitivity has been well documented, the functional significance of the
    Language English
    Publishing date 2023-06-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e16750
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: P681 mutations within the polybasic motif of spike dictate fusogenicity and syncytia formation of SARS CoV-2 variants

    Kuzmina, Alona / Atari, Nofar / Ottolenghi, Aner / Korovin, Dina / lass, Ido Cohen / Rosental, Benyamin / Rosenberg, Elli / Mandelboim, Michal / Taube, Ran

    bioRxiv

    Abstract: The rapid spread and dominance of the Omicron SARS-CoV-2 over its Delta variant has posed severe global challenges. While extensive research on the role of the Receptor Binding Domain on viral infectivity and vaccine sensitivity has been documented, the ... ...

    Abstract The rapid spread and dominance of the Omicron SARS-CoV-2 over its Delta variant has posed severe global challenges. While extensive research on the role of the Receptor Binding Domain on viral infectivity and vaccine sensitivity has been documented, the role of the spike <sub>681</sub>PRRAR/SV<sub>687</sub> polybasic motif is less clear. Here we monitored infectivity and vaccine sensitivity of Omicron SARS-CoV-2 pseudovirus against sera samples that were drawn four months post administration of the third dose of BNT162b2 mRNA vaccine. Our findings show that relative to Wuhan-Hu and Delta SARS-CoV-2, Omicron displayed enhanced infectivity and a sharp decline in its sensitivity to vaccine-induced neutralizing antibodies. Furthermore, while the spike proteins form Wuhan-Hu (P681), Omicron (H681) and BA.2 (H681) pseudoviruses modestly promoted cell fusion and syncytia formation, Delta spike (P681R) displayed enhanced fusogenic activity and syncytia formation capability. Live-viruses plaque formation assays confirmed these findings and demonstrated that relatively to the Wuhan-Hu and Omicron SARS-CoV-2, Delta formed more plaques that were smaller in size. Introducing a single P681R point mutation within the Wuhan-Hu spike, or H681R within Omicron spike, restored fusion potential to similar levels observed for Delta spike. Conversely, a R681P point mutation within Delta spike efficiency abolished fusion potential. We conclude that over time, the efficiency of the third dose of the Pfizer vaccine against SARS CoV-2 is waned, and cannot neutralize Omicron. We further verify that the P681 position of the viral spike dictates fusogenicity and syncytia formation.
    Keywords covid19
    Language English
    Publishing date 2022-04-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.04.26.489630
    Database COVID19

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