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    D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly

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    Type
    Preprint
    Authors
    Cavallo, Luigi cc
    Oliva, Romina cc
    KAUST Department
    Chemical Science Program
    KAUST Catalysis Center (KCC)
    Physical Science and Engineering (PSE) Division
    Date
    2020-06-09
    Permanent link to this record
    http://hdl.handle.net/10754/663703
    
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    Abstract
    AbstractThe iconic “red crown” of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made of its spike (S) glycoprotein. The S protein is the Trojan horse of coronaviruses, mediating their entry into the host cells. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On April 21$^{st}/$$, the GISAID resource had collected 10,823 SARS-CoV-2 genomic sequences. We extracted from them all the complete S protein sequences and identified point mutations thereof. Six mutations were located on a 14-residue segment (929-943) in the “fusion core” of the heptad repeat 1 (HR1). Our modeling in the pre- and post-fusion S protein conformations revealed, for three of them, the loss of interactions stabilizing the post-fusion assembly. On May 29$^{th}$$, the SARS-CoV-2 genomic sequences in GISAID were 34,805. An analysis of the occurrences of the HR1 mutations in this updated dataset revealed a significant increase for the S929I and S939F mutations and a dramatic increase for the D936Y mutation, which was particularly widespread in Sweden and Wales/England. We notice that this is also the mutation causing the loss of a strong inter-monomer interaction, the D936-R1185 salt bridge, thus clearly weakening the post-fusion assembly.
    Citation
    Cavallo, L., & Oliva, R. (2020). D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly. doi:10.1101/2020.06.08.140152
    Sponsors
    We gratefully acknowledge all the Authors from the Originating laboratories responsible for obtaining the specimens and the Submitting laboratories where genetic sequence data were generated and shared via the GISAID Initiative, on which this research is based. R.O. thanks MIUR-FFABR (Fondo per il Finanziamento Attività Base di Ricerca) for funding; L.C. acknowledge King Abdullah University of Science and Technology (KAUST) for support and the KAUST Supercomputing Laboratory for providing computational resources.
    Publisher
    Cold Spring Harbor Laboratory
    DOI
    10.1101/2020.06.08.140152
    Additional Links
    http://biorxiv.org/lookup/doi/10.1101/2020.06.08.140152
    ae974a485f413a2113503eed53cd6c53
    10.1101/2020.06.08.140152
    Scopus Count
    Collections
    Preprints; Physical Science and Engineering (PSE) Division; Chemical Science Program; KAUST Catalysis Center (KCC)

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