Uncovering the structural flexibility of SARS-CoV-2 glycoprotein spike variants

Abstract

The severe acute respiratory syndrome CoV-2 rapidly spread worldwide, causing a 43 pandemic. After a period of evolutionary stasis, a set of SARS-CoV-2 mutations has arisen in the 44 spike, the leading glycoprotein at the viral envelope and the primary antigenic candidate for 45 vaccines against the 2019 CoV disease (COVID-19). Here, we present comparative biochemical 46 data of the glycosylated full-length ancestral and D614G spike together with three other highly 47 transmissible strains classified by the World Health Organization as variants of concern (VOC): 48 beta, gamma, and delta. By showing that only D614G early variant has less hydrophobic surface 49 exposure and trimer persistence at mid-temperatures, we place D614G with features that support 50 a model of temporary fitness advantage for virus spillover worldwide. Further, during the SARS- 51 CoV-2 adaptation, the spike accumulates alterations leading to less structural rigidity.