Evolution of Sequence and Structure of SARS-CoV-2 Spike Protein: A Dynamic Perspective

Novel coronavirus (SARS-CoV-2) enters its host cell througha surfacespike protein. The viral spike protein has undergone several modifications/mutationsat the genomic level, through which it modulated its structure-functionand passed through several variants of concern. Recent advances inhigh-resolution structure determination and multiscale imaging techniques,cost-effective next-generation sequencing, and development of newcomputational methods (including information theory, statistical methods,machine learning, and many other artificial intelligence-based techniques)have hugely contributed to the characterization of sequence, structure,function of spike proteins, and its different variants to understandviral pathogenesis, evolutions, and transmission. Laying on the foundationof the sequence-structure-function paradigm, this reviewsummarizes not only the important findings on structure/functionbut also the structural dynamics of different spike components, highlightingthe effects of mutations on them. As dynamic fluctuations of three-dimensionalspike structure often provide important clues for functional modulation,quantifying time-dependent fluctuations of mutational events overspike structure and its genetic/amino acidic sequence helps identifyalarming functional transitions having implications for enhanced fusogenicityand pathogenicity of the virus. Although these dynamic events aremore difficult to capture than quantifying a static, average property,this review encompasses those challenging aspects of characterizingthe evolutionary dynamics of spike sequence and structure and theirimplications for functions.