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Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation

View ORCID ProfileDavid P. Maison, View ORCID ProfileLauren L. Ching, Cecilia M. Shikuma, View ORCID ProfileVivek R. Nerurkar
doi: https://doi.org/10.1101/2021.01.06.425497
David P. Maison
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
2Pacific Center for Emerging Infectious Diseases Research, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
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Lauren L. Ching
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
2Pacific Center for Emerging Infectious Diseases Research, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
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Cecilia M. Shikuma
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
3Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
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Vivek R. Nerurkar
1Department of Tropical Medicine, Medical Microbiology, and Pharmacology, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
2Pacific Center for Emerging Infectious Diseases Research, University of Hawai□i at Mānoa, Honolulu, Hawaii 96813
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  • For correspondence: nerurkar@hawaii.edu
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Abstract

COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in the first year, and severely affected the global economy. Hawaii is not spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Early in the pandemic, we described in this journal various technologies used for the detection of SARS-CoV-2. Herein we characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain. At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from two patients from Hawaii who were infected with the SARS-CoV-2 in August 2020. Following PCR, the two viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawaii from multiple sources. Further, we decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with one non-synonymous mutation (P681H) found in the two Hawaii strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation. The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawaii.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    ASGPB
    Advanced Studies in Genomics, Proteomics, and Bioinformatics
    A1708D
    Alanine to Aspartic Acid at Amino Acid 1708
    A570D
    Alanine to Aspartic Acid at Amino Acid 570
    A522S
    Alanine to Serine at Amino Acid 522
    A771S
    Alanine to Serine at Amino Acid 771
    ACE2
    Angiotensin-Converting Enzyme 2
    R577C
    Arginine to Cysteine at Amino Acid 577
    R52I
    Arginine to Isoleucine at Amino Acid 52
    N501Y
    Asparagine to Tyrosine at Amino Acid 501
    D614G
    Aspartic Acid to Glycine at Amino Acid 614
    D1118H
    Aspartic Acid to Histidine at Amino Acid 1118
    D3L
    Aspartic Acid to Leucine at Amino Acid 3
    cDNA
    complementary deoxyribonucleic acid
    COVID-19
    Coronavirus Disease 2019
    ΔG2676
    deletion of Glycine Amino Acid 2676
    ΔH69
    deletion of Histidine Amino Acid 69
    ΔF3677
    deletion of Phenylalanine Amino Acid 3677
    ΔS3675
    deletion of Serine Amino Acid 3675
    ΔY145
    deletion of Tyrosine Amino Acid 145
    ΔV70
    deletion of Valine Amino Acid 70
    DNA
    deoxyribonucleic acid
    EUA
    Emergency Use Authorization
    GISAID
    Global Initiative of Sharing All Influenza Data
    E780Q
    Glutamic Acid to Glutamine at Amino Acid 780
    Q27stop
    Glutamine to stop codon at Amino Acid 27
    IBC
    Institutional Biosafety Committee
    IRB
    Institutional Review Board
    I726F
    Isoleucine to Phenylalanine at Amino Acid 726
    I2230T
    Isoleucine to Threonine at Amino Acid 2230
    I584V
    Isoleucine to Valine at Amino Acid 584
    MUSCLE
    Multiple Sequence Comparison by Log-Expectation
    NCBI
    National Center for Biotechnology Information
    NERVTAG
    New and Emerging Respiratory Virus Threats Advisory Group
    nCoV
    novel coronavirus
    PID
    Patient Identification
    F797C
    Phenylalanine to Cysteine at Amino Acid 797
    F543L
    Phenylalanine to Leucine at Amino Acid 543
    PCR
    Polymerase Chain Reaction
    P681H
    Proline to Histidine at Amino Acid 681
    RBD
    Receptor Binding Domain
    RT-PCR
    reverse transcriptase Polymerase Chain Reaction
    RNA
    ribonucleic acid
    S982A
    Serine to Alanine at Amino Acid 982
    S680C
    Serine to Cysteine at Amino Acid 680
    S235F
    Serine to Phenylalanine at Amino Acid 235
    SARS-CoV-2
    Severe Acute Respiratory Syndrome Coronavirus 2
    SNP
    Single Nucleotide Polymorphism
    T1001I
    Threonine to Isoleucine at Amino Acid 1001
    T716I
    Threonine to Isoleucine at Amino Acid 716
    TBE
    Tris/Borate/Ethylenediaminetetraacetic acid
    Y73C
    Tyrosine to Cysteine at Amino Acid 73
    FDA
    United State Food and Drug Administration
    VOC
    Variant of Concern
    VTM
    Viral Transport Media
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    Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation
    David P. Maison, Lauren L. Ching, Cecilia M. Shikuma, Vivek R. Nerurkar
    bioRxiv 2021.01.06.425497; doi: https://doi.org/10.1101/2021.01.06.425497
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    Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation
    David P. Maison, Lauren L. Ching, Cecilia M. Shikuma, Vivek R. Nerurkar
    bioRxiv 2021.01.06.425497; doi: https://doi.org/10.1101/2021.01.06.425497

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