Structural insights on the differentiation and reversion of conformational changes in SARS-CoV-2 spike protein models across variants occurring from December, 2019 to November, 2021

Abstract

Conformational changes in the SARS-CoV-2 spike protein are critical for understanding viral evolution. In this study, we provide comparative structural and electrostatic analyses across variants, revealing both differentiation and reversion patterns not previously described in locked and activated spike conformations. More specifically, we generated SARS2 spike protein models from the various recorded variants between December, 2019 and November 2021, and performed structural superimposition, dendrogram analyses, and electrostatic mapping. We confirmed which locked and activated conformations differed and reversed between the Original spike protein model and subsequent SARS2 variants and subvariants. Additionally, among the spike protein models of subsequent SARS2 variants and subvariants during December, 2019-November, 2021, we likewise established structural variations and reversions among the locked and activated conformations. Moreover, we established the structural relationship and clustering among the locked and activated conformations of the SARS2 spike protein models. Furthermore, we determined the electrostatic potential of all generated SARS2 spike protein models to establish the surface charge distribution. Taken together, we found that certain locked and activated conformations of the Original SARS2 spike protein models exhibited both structural differences and, surprisingly, reversion when compared to subsequent variants and subvariants. Similarly, structural differentiation and reversion were also observed in the locked and activated conformations across the spike protein models. Additionally, we identified distinct structural clusters within the locked and activated conformations, establishing a structural relationship among certain SARS2 spike protein models. Moreover, we found that during spike evolution reorganization of the surface charge distribution occurs during structural differentiation and reversion.