Version 1
: Received: 7 July 2024 / Approved: 8 July 2024 / Online: 8 July 2024 (08:35:41 CEST)
How to cite:
Ali, M. A.; Anollés, G. C.-. AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants. Preprints2024, 2024070591. https://doi.org/10.20944/preprints202407.0591.v1
Ali, M. A.; Anollés, G. C.-. AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants. Preprints 2024, 2024070591. https://doi.org/10.20944/preprints202407.0591.v1
Ali, M. A.; Anollés, G. C.-. AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants. Preprints2024, 2024070591. https://doi.org/10.20944/preprints202407.0591.v1
APA Style
Ali, M. A., & Anollés, G. C. . (2024). AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants. Preprints. https://doi.org/10.20944/preprints202407.0591.v1
Chicago/Turabian Style
Ali, M. A. and Gustavo Caetano- Anollés. 2024 "AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants" Preprints. https://doi.org/10.20944/preprints202407.0591.v1
Abstract
The COVID 19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until July 23, 2023. Since the 3-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention.
Keywords
COVID-19; haplotypes; nucleocapsid protein; mutation; pandemic; protein structure; recruitment; variant of concern; virus evolution
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.