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

• Published in: Nature communications Vol. 13; no. 1; p. 222
• Main Authors: Gupta, Kapil, Toelzer, Christine, Williamson, Maia Kavanagh, Shoemark, Deborah K., Oliveira, A. Sofia F., Matthews, David A., Almuqrin, Abdulaziz, Staufer, Oskar, Yadav, Sathish K. N., Borucu, Ufuk, Garzoni, Frederic, Fitzgerald, Daniel, Spatz, Joachim, Mulholland, Adrian J., Davidson, Andrew D., Schaffitzel, Christiane, Berger, Imre
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 13/106; 631/45/612/1256; 631/535/1258/1259; 631/535/1267; 82/103; 82/58; 82/80; 82/83; ACE2; Allosteric properties; Amino acids; Angiotensin-converting enzyme 2; Animals; Cell Line; Cleavage; Clonal deletion; COVID-19 - virology; Cryoelectron Microscopy; Deletion; Evolution; Evolution, Molecular; Furin; Furin - metabolism; Genetic diversity; Humanities and Social Sciences; Humans; Infectivity; Linoleic Acid - metabolism; Molecular dynamics; Molecular Dynamics Simulation; Molecular structure; multidisciplinary; Mutation; Protein Binding; Protein Conformation; RNA viruses; SARS-CoV-2 - chemistry; SARS-CoV-2 - genetics; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Structure-function relationships; Tropism; Viral diseases; Viral Tropism; Virus Internalization; Viruses; United Kingdom > UK; England
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27881-6

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. BriSΔ, a SARS-CoV-2 variant from clinical isolate hCoV/England/02/2020, comprises a deletion in a spike cleavage site. The structure and molecular dynamics of this spike provides mechanistic insights into how the deletion modulates virus infectivity.