Conformational stability of SARS-CoV-2 glycoprotein spike variants

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. [Display omitted] •Comparative biochemical data of the ancestral, D614G, beta, gamma, and delta spikes•D614G has less hydrophobic exposure and trimer persistence at mid temperatures•The ancestral and gamma spikes have similar glycan abundance•SARS-CoV-2 evolution alters the spike stability for some variants Biochemistry; Virology; Structural biology; Protein structure aspects