Genetic Variants of SARS-CoV-2—What Do They Mean? | Infectious Diseases | JAMA | JAMA Network
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January 6, 2021

Genetic Variants of SARS-CoV-2—What Do They Mean?

Author Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan, Ann Arbor
  • 2Institute of Social and Preventive Medicine, University of Bern, Switzerland
JAMA. Published online January 6, 2021. doi:10.1001/jama.2020.27124

Over the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the clinical, scientific, and public health communities have had to respond to new viral genetic variants. Each one has triggered a flurry of media attention, a range of reactions from the scientific community, and calls from governments to either “stay calm” or pursue immediate countermeasures. While many scientists were initially skeptical about the significance of the D614G alteration, the emergence of the new “UK variant”—lineage B.1.1.7—has raised widespread concern. Understanding which variants are concerning, and why, requires an appreciation of virus evolution and the genomic epidemiology of SARS-CoV-2.

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    2 Comments for this article
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    Effect of SARS-CoV-2 (Y453F) variant on COVID-19 vaccine
    Takuma Hayashi, MBBS, DMSci, GMRC, PhD. | National Hospital Organization Kyoto Medical Center
    Mustelidae animals such as mink and ferrets can be infected with SARS-CoV-2 relatively easily compared to other mammals. It is not clear why SARS-CoV-2 is so contagious to these animals (1). It is clear that when farmed minks are kept in large quantities in a high density environment, SARS-CoV-2 proliferates in large quantities in the mink body. As a result, farmed mink as well as humans may easily transmit SARS-CoV-2.

    Natural selection “adaptation” in the coronavirus can occur during coronavirus amplification in vivo in farmed mink (2). Natural selection in such viruses is observed by the appearance of mutations
    in SARS-CoV-2 that are not observed during the growth process in humans (2,3). Infection with a mutant (Y453F) of SARS-CoV-2 from farmed mink is widespread among people (4).

    Recent studies summarized in a preprint (5) have revealed the following:

    • The Y453F mutation does not affect the three-dimensional structure of conventional SARS-CoV-2 spike glycoproteins. It was clarified that the binding property of the spike glycoprotein Y453F mutant to human ACE2 was slightly weaker than that of the conventional SARS-CoV-2 spike glycoprotein. It was revealed that the affinity between the spike glycoprotein Y453F mutant and 4 of the 6 neutralizing antibodies examined was clearly weak compared to the conventional SARS-CoV-2 spike glycoprotein.
    • Affinity between the appropriate amino acid residues in the variable region of the antibody and the spike glycoprotein RBD F453 has diminished as cause of weak recognition of monoclonal antibodies for spike glycoproteins. Subspecies of SARS-CoV-2 derived from farmed mink has been observed in samples from infected people; the virus mutants are inherited by infected individuals.
    • Since the mutations have occurred in SARS-CoV-2, subspecies of SARS-CoV-2, which are susceptible to human and animal infection, easily propagate in the host. The spread of SARS-CoV-2 variants mediated by millions of farmed minks is uncontrolled. As a result, there is concern that SARS-CoV-2 mutants, which cause serious symptoms in humans, may be spread all over the world.

    Acknowledgments

    We thank all the medical staffs and co-medical staffs for providing and helping medical research at National Hospital Organization Kyoto Medical Center.

    Reference
    1. Enserink M. Science 368(6496): 1169 (2020)
    2. Oude Munnink BB. et al. Science DOI: 10.1126/science.abe5901
    3. Hayashi T. Konishi I. Science https://science.sciencemag.org/content/368/6496/1169/tab-e-letters
    4. Mallapaty S. Nature 587(7834): 340-341 (2020).
    5. Hayashi T. et al. bioRxiv Cold Spring Harbor https://www.biorxiv.org/content/10.1101/2020.11.27.401893v1
    CONFLICT OF INTEREST: None Reported
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    Immunity to CoVID variants
    Camilo Colaco, PhD | ImmBio, Founder and Chief Scientific Officer
    While much attention is being focused on escape from neutralizing antibody induced by vaccine, it should be noted that T-cells also contribute to vaccine-induced immunity. Moreover with regard to potential effects of genetic variants of Spike protein, it is important to remember that the major anti-viral immunity to CoVID19 is the interferon mediated innate immune response.

    Disclosure: ImmBio, Chief Scientific Officer
    CONFLICT OF INTEREST: None Reported
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