Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2

Kapil Gupta (), Christine Toelzer, Maia Kavanagh Williamson, Deborah K. Shoemark, A. Sofia F. Oliveira, David A. Matthews, Abdulaziz Almuqrin, Oskar Staufer, Sathish K. N. Yadav, Ufuk Borucu, Frederic Garzoni, Daniel Fitzgerald, Joachim Spatz, Adrian J. Mulholland, Andrew D. Davidson, Christiane Schaffitzel () and Imre Berger ()
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Kapil Gupta: University of Bristol
Christine Toelzer: University of Bristol
Maia Kavanagh Williamson: University of Bristol, University Walk
Deborah K. Shoemark: University of Bristol
A. Sofia F. Oliveira: University of Bristol
David A. Matthews: University of Bristol, University Walk
Abdulaziz Almuqrin: University of Bristol, University Walk
Oskar Staufer: Max Planck Institute for Medical Research
Sathish K. N. Yadav: University of Bristol
Ufuk Borucu: University of Bristol
Frederic Garzoni: Albert Rd, St. Philips
Daniel Fitzgerald: Albert Rd, St. Philips
Joachim Spatz: Max Planck Institute for Medical Research
Adrian J. Mulholland: University of Bristol, Cantock’s Close
Andrew D. Davidson: University of Bristol, University Walk
Christiane Schaffitzel: University of Bristol
Imre Berger: University of Bristol

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.

Date: 2022
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DOI: 10.1038/s41467-021-27881-6

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