Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants

View ORCID ProfileVeronika Tchesnokova, Hemantha Kulakesara, Lydia Larson, Victoria Bowers, Elena Rechkina, Dagmara Kisiela, Yulia Sledneva, Debarati Choudhury, Iryna Maslova, Kai Deng, Kirthi Kutumbaka, Hao Geng, Curtis Fowler, Dina Greene, James Ralston, Mansour Samadpour, Evgeni Sokurenko
doi: https://doi.org/10.1101/2021.02.22.432189
Veronika Tchesnokova
1University of Washington, Seattle, WA
2ID Genomics, Inc., Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Veronika Tchesnokova
Hemantha Kulakesara
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lydia Larson
1University of Washington, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Victoria Bowers
4ARMADA (The Antibiotic Resistance Monitoring, Analysis and Diagnostics Alliance), Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elena Rechkina
2ID Genomics, Inc., Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dagmara Kisiela
1University of Washington, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yulia Sledneva
2ID Genomics, Inc., Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Debarati Choudhury
2ID Genomics, Inc., Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iryna Maslova
2ID Genomics, Inc., Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kai Deng
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirthi Kutumbaka
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hao Geng
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Curtis Fowler
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dina Greene
5Kaiser Permanente Washington (KPWA) and KPWA Research Institute, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Ralston
5Kaiser Permanente Washington (KPWA) and KPWA Research Institute, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mansour Samadpour
3IEH Laboratories and Consulting Group, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Evgeni Sokurenko
1University of Washington, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: evs@uw.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The recent rise in mutational variants of SARS-CoV-2, especially with changes in the Spike protein, is of significant concern due to the potential ability for these mutations to increase viral infectivity, virulence and/or ability to escape protective antibodies. Here, we investigated genetic variations in a 414-583 amino acid region of the Spike protein, partially encompassing the ACE2 receptor-binding domain (RBD), across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with a recently discovered CAL.20C viral variant from clade 20C, lineage B.1.429, that since November-December 2020 is associated with multiple outbreaks and is undergoing massive expansion across California. In some samples, however, we found a distinct L452R-carrying variant of the virus that, upon detailed analysis of the GISAID database genomes, is also circulating primarily in California, but emerged even more recently. The newly identified variant derives from the clade 20A (lineage B.1.232) and is named CAL.20A. We also found that the SARS-CoV-2 strain that caused the only recorded case of infection in an ape - gorillas in the San Diego Zoo, reported in January 2021 - is CAL.20A. In contrast to CAL.20C that carries two additional to L452R mutations in the Spike protein, L452R is the only mutation found in CAL.20A. According to the phylogenetic analysis, however, emergence of CAL.20C was also specifically triggered by acquisition of the L452R mutation. Further analysis of GISAID-deposited genomes revealed that several independent L452R-carrying lineages have recently emerged across the globe, with over 90% of the isolates reported between December 2020 - February 2021. Taken together, these results indicate that the L452R mutation alone is of significant adaptive value to SARS-CoV-2 and, apparently, the positive selection for this mutation became particularly strong only recently, possibly reflecting viral adaptation to the containment measures or increasing population immunity. While the functional impact of L452R has not yet been extensively evaluated, leucine-452 is positioned in the receptor-binding motif of RBD, in the interface of direct contact with the ACE2 receptor. Its replacement with arginine is predicted to result in both a much stronger binding to the receptor and escape from neutralizing antibodies. If true, this in turn might lead to significantly increased infectivity of the L452R variants, warranting their close surveillance and in-depth functional studies.

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.
Back to top
PreviousNext
Posted February 22, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
Veronika Tchesnokova, Hemantha Kulakesara, Lydia Larson, Victoria Bowers, Elena Rechkina, Dagmara Kisiela, Yulia Sledneva, Debarati Choudhury, Iryna Maslova, Kai Deng, Kirthi Kutumbaka, Hao Geng, Curtis Fowler, Dina Greene, James Ralston, Mansour Samadpour, Evgeni Sokurenko
bioRxiv 2021.02.22.432189; doi: https://doi.org/10.1101/2021.02.22.432189
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
Veronika Tchesnokova, Hemantha Kulakesara, Lydia Larson, Victoria Bowers, Elena Rechkina, Dagmara Kisiela, Yulia Sledneva, Debarati Choudhury, Iryna Maslova, Kai Deng, Kirthi Kutumbaka, Hao Geng, Curtis Fowler, Dina Greene, James Ralston, Mansour Samadpour, Evgeni Sokurenko
bioRxiv 2021.02.22.432189; doi: https://doi.org/10.1101/2021.02.22.432189

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4114)
  • Biochemistry (8816)
  • Bioengineering (6519)
  • Bioinformatics (23464)
  • Biophysics (11792)
  • Cancer Biology (9209)
  • Cell Biology (13325)
  • Clinical Trials (138)
  • Developmental Biology (7439)
  • Ecology (11412)
  • Epidemiology (2066)
  • Evolutionary Biology (15152)
  • Genetics (10439)
  • Genomics (14044)
  • Immunology (9172)
  • Microbiology (22159)
  • Molecular Biology (8813)
  • Neuroscience (47575)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3730)
  • Plant Biology (8082)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1253)