Conformational stability of SARS-CoV-2 glycoprotein spike variants

Hiam R.S. Arruda; Tulio M. Lima; Renata G.F. Alvim; Fernanda B.A. Victorio; Daniel P.B. Abreu; Federico F. Marsili; Karen D. Cruz; Mayra A. Marques; Patricia Sosa-Acosta; Mauricio Quinones-Vega; Jéssica de S. Guedes; Fábio C.S. Nogueira; Jerson L. Silva; Leda R. Castilho; Guilherme A.P. de Oliveira

iScience (Jan 2023)

Conformational stability of SARS-CoV-2 glycoprotein spike variants

Hiam R.S. Arruda,
Tulio M. Lima,
Renata G.F. Alvim,
Fernanda B.A. Victorio,
Daniel P.B. Abreu,
Federico F. Marsili,
Karen D. Cruz,
Mayra A. Marques,
Patricia Sosa-Acosta,
Mauricio Quinones-Vega,
Jéssica de S. Guedes,
Fábio C.S. Nogueira,
Jerson L. Silva,
Leda R. Castilho,
Guilherme A.P. de Oliveira

Affiliations

Hiam R.S. Arruda: Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Tulio M. Lima: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil; EPQB Program, School of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598 Brazil
Renata G.F. Alvim: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil
Fernanda B.A. Victorio: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil
Daniel P.B. Abreu: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil
Federico F. Marsili: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil; Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil
Karen D. Cruz: Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Mayra A. Marques: Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Patricia Sosa-Acosta: Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil; Laboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-598, Brazil
Mauricio Quinones-Vega: Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil; Laboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-598, Brazil
Jéssica de S. Guedes: Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil; Laboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-598, Brazil
Fábio C.S. Nogueira: Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil; Laboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-598, Brazil
Jerson L. Silva: Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Leda R. Castilho: Cell Culture Engineering Laboratory, COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-598, Brazil; Biochemistry Program, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ 21941-909, Brazil; Corresponding author
Guilherme A.P. de Oliveira: Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Corresponding author

Journal volume & issue: Vol. 26, no. 1
p. 105696

Abstract

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Summary: The severe acute respiratory syndrome spread worldwide, causing a pandemic. SARS-CoV-2 mutations have arisen in the spike, a glycoprotein at the viral envelope and an antigenic candidate for vaccines against COVID-19. Here, we present comparative data of the glycosylated full-length ancestral and D614G spike together with three other transmissible strains classified by the World Health Organization as variants of concern: beta, gamma, and delta. By showing that D614G has less hydrophobic surface exposure and trimer persistence, we place D614G with features that support a model of temporary fitness advantage for virus spillover. Furthermore, during the SARS-CoV-2 adaptation, the spike accumulates alterations leading to less structural stability for some variants. The decreased trimer stability of the ancestral and gamma and the presence of D614G uncoupled conformations mean higher ACE-2 affinities compared to the beta and delta strains. Mapping the energetics and flexibility of variants is necessary to improve vaccine development.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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