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Evolutionary tracking of SARS-CoV-2 genetic variants highlights an intricate balance of stabilizing and destabilizing mutations

Jobin John Jacob, Karthick Vasudevan, Agila Kumari Pragasam, Karthik Gunasekaran, Balaji Veeraraghavan, Ankur Mutreja
doi: https://doi.org/10.1101/2020.12.22.423920
Jobin John Jacob
1Department of Clinical Microbiology, Christian Medical College, Vellore, India
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Karthick Vasudevan
1Department of Clinical Microbiology, Christian Medical College, Vellore, India
4Department of Biotechnology, School of Applied Sciences, REVA University, Bangalore, India
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Agila Kumari Pragasam
1Department of Clinical Microbiology, Christian Medical College, Vellore, India
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Karthik Gunasekaran
2Department of General Medicine (Unit-V), Christian Medical College, Vellore, India
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Balaji Veeraraghavan
1Department of Clinical Microbiology, Christian Medical College, Vellore, India
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  • For correspondence: am872@medschl.cam.ac.uk vbalaji@cmcvellore.ac.in
Ankur Mutreja
3Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, University of Cambridge, Cambridge, UK
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  • For correspondence: am872@medschl.cam.ac.uk vbalaji@cmcvellore.ac.in
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ABSTRACT

The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of this genome datasets has allowed unprecedented access into the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage defining mutations were analysed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X) and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount soon in coming months, the task of mapping of viral mutations and recording of their impact on key viral proteins would be crucial to pre-emptively catch any escape mechanism that SARS-CoV-2 may evolve for.

STUDY IMPORTANCE As large numbers of the SARS CoV-2 genome sequences are shared in publicly accessible repositories, it enables scientists a detailed evolutionary analysis since its initial isolation in Wuhan, China. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines recently approved and in development. In this direction, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 16, 2021.
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Evolutionary tracking of SARS-CoV-2 genetic variants highlights an intricate balance of stabilizing and destabilizing mutations
Jobin John Jacob, Karthick Vasudevan, Agila Kumari Pragasam, Karthik Gunasekaran, Balaji Veeraraghavan, Ankur Mutreja
bioRxiv 2020.12.22.423920; doi: https://doi.org/10.1101/2020.12.22.423920
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Evolutionary tracking of SARS-CoV-2 genetic variants highlights an intricate balance of stabilizing and destabilizing mutations
Jobin John Jacob, Karthick Vasudevan, Agila Kumari Pragasam, Karthik Gunasekaran, Balaji Veeraraghavan, Ankur Mutreja
bioRxiv 2020.12.22.423920; doi: https://doi.org/10.1101/2020.12.22.423920

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