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International Conference on Computer Science Protecting Human Society Against Epidemics

ANTICOVID 2021: Computer Science Protecting Human Society Against Epidemics pp 1–13Cite as

Bioinformatic and MD Analysis of N501Y SARS-CoV-2 (UK) Variant

Part of the IFIP Advances in Information and Communication Technology book series (IFIPAICT,volume 616)

Abstract

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pathogen. Although a number of new vaccines are available to combat this threat, a high prevalence of novel mutant viral variants is observed in all world regions affected by this infection. Among viral proteomes, the highly glycosylated spike protein (Sprot) of SARS-CoV-2 has received the most attention due to its interaction with the host receptor ACE2. To understand the mechanisms of viral variant infectivity and the interaction of the RBD of Sprot with the host ACE2, we performed a large-scale mutagenesis study of the RBD-ACE2 interface by performing 1780 point mutations in silico and identifying the ambiguous stabilisation of the interface by the most common point mutations described in the literature. Furthermore, we pinpointed the N501Y mutation at the RBD of Sprot as profoundly affecting complex formation and confirmed greater stability of the N501Y mutant compared to wild-type (WT) viral S protein by molecular dynamics experiments. These findings could be important for the study and design of upcoming vaccines, PPI inhibitor molecules, and therapeutic antibodies or antibody mimics.

Keywords

  • COVID-19
  • SARS-CoV-2
  • Point mutation
  • SARS-CoV-2 variants
  • Protein-protein interactions
  • Drug design

Supported by the Slovenian Ministry of Science and Education infrastructure project grant HPC-RIVR, by the Slovenian Research Agency (ARRS) programme and project grants P2-0046 and J1-2471, and by Slovenian Ministry of Education, Science and Sports programme grant OP20.04342.

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Abbreviations

ACE2:

Angiotensin-converting enzyme 2

MD:

Molecular Dynamics

PDB:

Protein Data Bank

PPI:

Protein-Protein Interactions

RBD:

Receptor Binding Domain

WHO:

World Health Organisation

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Acknowledgements

We thank Javier Delgado Blanco and Luis Serrano Pubul from FoldX for their support. Heartfelt thanks to Črtomir Podlipnik, a friend and a scientific colleague.

Thank You, participants in the COVID.SI community ( www.co-vid.si and www.sidock.si ) for supporting our work. Thank You All!

Author information

Authors and Affiliations

  1. Faculty of Chemistry and Chemical Engineering, Laboratory of Physical Chemistry and Chemical Thermodynamics, University of Maribor, Smetanova ulica 17, 2000, Maribor, Slovenia

    Marko Jukić, Sebastjan Kralj & Urban Bren

  2. Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000, Koper, Slovenia

    Marko Jukić & Urban Bren

  3. Research Center of the Russian Academy of Sciences, Institute of Applied Mathematical Research, Karelian, Pushkinskaya 11, 185910, Petrozavodsk, Russia

    Natalia Nikitina

Authors
  1. Marko Jukić
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  2. Sebastjan Kralj
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  3. Natalia Nikitina
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  4. Urban Bren
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Corresponding authors

Correspondence to Marko Jukić or Urban Bren .

Editor information

Editors and Affiliations

  1. AGH University of Science and Technology, Kraków, Poland

    Aleksander Byrski

  2. Institute of Theoretical and Applied Informatics, Polish Academy of Sciences, Gliwice, Poland

    Prof. Tadeusz Czachórski

  3. Institute of Theoretical and Applied Informatics, Polish Academy of Sciences, Gliwice, Poland

    Erol Gelenbe

  4. Institute of Theoretical and Applied Informatics, Polish Academy of Sciences, Gliwice, Poland

    Dr. Krzysztof Grochla

  5. Tsuda University, Tokyo, Japan

    Prof. Dr. Yuko Murayama

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Jukić, M., Kralj, S., Nikitina, N., Bren, U. (2021). Bioinformatic and MD Analysis of N501Y SARS-CoV-2 (UK) Variant. In: Byrski, A., Czachórski, T., Gelenbe, E., Grochla, K., Murayama, Y. (eds) Computer Science Protecting Human Society Against Epidemics. ANTICOVID 2021. IFIP Advances in Information and Communication Technology, vol 616. Springer, Cham. https://doi.org/10.1007/978-3-030-86582-5_1

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  • DOI: https://doi.org/10.1007/978-3-030-86582-5_1

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  • Online ISBN: 978-3-030-86582-5

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