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dc.contributor.authorCavallo, Luigi
dc.contributor.authorOliva, Romina
dc.date.accessioned2020-06-18T13:24:32Z
dc.date.available2020-06-18T13:24:32Z
dc.date.issued2020-06-09
dc.identifier.citationCavallo, 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
dc.identifier.doi10.1101/2020.06.08.140152
dc.identifier.urihttp://hdl.handle.net/10754/663703
dc.description.abstractAbstractThe 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.
dc.description.sponsorshipWe 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.
dc.publisherCold Spring Harbor Laboratory
dc.relation.urlhttp://biorxiv.org/lookup/doi/10.1101/2020.06.08.140152
dc.rightsArchived with thanks to Cold Spring Harbor Laboratory
dc.titleD936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly
dc.typePreprint
dc.contributor.departmentChemical Science Program
dc.contributor.departmentKAUST Catalysis Center (KCC)
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.eprint.versionPre-print
dc.contributor.institutionDepartment of Sciences and Technologies, University Parthenope of Naples, Centro Direzionale Isola C4, I-80143, Naples, Italy.
kaust.personCavallo, Luigi
refterms.dateFOA2020-06-18T13:24:54Z
kaust.acknowledged.supportUnitKAUST Supercomputing Laboratory


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