Charge Matters: Mutations in Omicron Variant Favor Binding to Cells. (2nd February 2022)

• Record Type: Journal Article
• Authors: Nie, Chuanxiong; Sahoo, Anil Kumar; Netz, Roland R.; Herrmann, Andreas; Ballauff, Matthias; Haag, Rainer
• Is Part Of: Chembiochem. Volume 23:Number 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202100681
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Evidence is strengthening to suggest that the novel SARS‐CoV‐2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide. Although the mutations in the spike protein are known, the molecular basis for why the additional mutations in the spike protein that have not previously occurred account for Omicron's higher infection potential, is not understood. We propose, based on chemical rational and molecular dynamics simulations, that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs. wild type) increases binding to cellular polyanionic receptors, such as heparan sulfate due to multivalent charge‐charge interactions. This observation is a starting point for targeted drug development. Abstract : Because of the mutations present in the Omicron variant, the surface of the spike protein is highly positively charged. For binding of SARS‐CoV‐2 to host cells, electrostatic interactions with heparan sulfate polyglycerols covering the cell surface play an essential role. Molecular dynamic simulation reveals that the interaction of the Omicron spike with polysulfates is much stronger than that of the wild type. We surmise that this enhanced interaction favors binding of Omicron and therefore subsequent cell entry and infection.