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Endogenous currents in HEK 293 cells are inhibited by memantine

Nature Chemical Biology volume 19, pages 1303–1305 (2023)Cite this article

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Matters Arising to this article was published on 05 October 2023

The Original Article was published on 29 September 2022

arising from C. Oh et al. Nature Chemical Biology https://doi.org/10.1038/s41589-022-01149-6 (2023)

We write in reference to the recent work of Oh et al.1, which suggests that adamantanes, such as amantadine and memantine, may interact with viral ion channels and might have therapeutic use in COVID-19. We concur with the idea that the E protein of SARS-CoV-2 can form an ion channel and that amantadine is an inhibitor of this channel2, but we suggest caution in the interpretation of some results reported in this paper. In their fig. 5c, Oh et al.1 show the purported ‘viroporin’ current recorded from the plasma membrane (PM) of human embryonic kidney (HEK) 293 cells expressing the viral E protein, and then show in their fig. 5f that the current is inhibited by memantine and NMT5. There are several concerns with these data:

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Fig. 1

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All data are available from the corresponding author upon request.

References

  1. Oh, C. et al. Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nat. Chem. Biol. 19, 275–283 (2023).

    Article  CAS  PubMed  Google Scholar 

  2. Harrison, N. L. et al. How many SARS-CoV-2 ‘viroporins’ are really ion channels? Commun. Biol. 5, 859 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cohen, J. R., Lin, L. D. & Machamer, C. E. Identification of a Golgi complex-targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein. J. Virol. 85, 5794–5803 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cabrera-Garcia, D., Bekdash, R., Abbott, G. W., Yazawa, M. & Harrison, N. L. The envelope protein of SARS-CoV-2 increases intra-Golgi pH and forms a cation channel that is regulated by pH. J. Physiol. 599, 2851–2868 (2021).

    Article  CAS  PubMed  Google Scholar 

  5. Schulze, T. et al. SARS-CoV-2 envelope-protein corruption of homeostatic signaling mechanisms in mammalian cells. Preprint at bioRxiv https://doi.org/10.1101/2021.06.16.448640 (2021).

  6. Breitinger, U., Ali, N. K. M., Sticht, H. & Breitinger, H.-G. Inhibition of SARS CoV envelope protein by flavonoids and classical viroporin inhibitors. Front. Microbiol. 12, 692423 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ponce, A., Castillo, A., Hinojosa, L., Martinez-Rendon, J. & Cereijido, M. The expression of endogenous voltage-gated potassium channels in HEK293 cells is affected by culture conditions. Physiol. Rep. 6, e13663 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lowinus, T. et al. Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of Kv1.3 potassium channels, AKT and ERK1/2 signaling. Cell Commun. Signal. 17, 5 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  9. McClenaghan, C., Hanson, A., Lee, S.-J. & Nichols, C. G. Coronavirus proteins as ion channels: current and potential research. Front. Immunol. 11, 573339 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Anesthesiology, Columbia University, New York, NY, USA

    Neil L. Harrison

  2. Departments of Anesthesiology and Molecular Pharmacology and Therapeutics, Columbia University, New York, NY, USA

    Neil L. Harrison

  3. Department of Physiology and Biophysics, University of California at Irvine, Irvine, CA, USA

    Geoffrey W. Abbott

  4. Center for Advanced Biotechnology and Medicine and Departments of Pharmacology and Medicine, Robert Wood Johnson School of Medicine, Rutgers University, Piscataway, NJ, USA

    Conor McClenaghan

  5. Center for the Investigation of Membrane Excitability Diseases, and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA

    Colin G. Nichols

  6. Netherlands Institute for Neuroscience, Amsterdam, the Netherlands

    David Cabrera-Garcia

Authors
  1. Neil L. Harrison
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  2. Geoffrey W. Abbott
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  4. Colin G. Nichols
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  5. David Cabrera-Garcia
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Contributions

N.L.H. conceived the letter and wrote the first draft of the manuscript. C.M. performed the memantine experiments. D.C.G. performed confocal microscopy, E protein current and endogenous current recordings. G.W.A. and C.G.N. contributed to literature review, data analysis and interpretation. All authors commented on and edited the final manuscript.

Corresponding author

Correspondence to Neil L. Harrison.

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The authors declare no competing interests.

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Nature Chemical Biology thanks Stephen Griffin, Yasuo Mori and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Harrison, N.L., Abbott, G.W., McClenaghan, C. et al. Endogenous currents in HEK 293 cells are inhibited by memantine. Nat Chem Biol 19, 1303–1305 (2023). https://doi.org/10.1038/s41589-023-01423-1

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