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
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.
