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Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection

Nature Chemical Biology volume 19, pages 1306–1308 (2023)Cite this article

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The Original Article was published on 05 October 2023

replying to N. L. Harrison et al. Nature Chemical Biology https://doi.org/10.1038/s41589-023-01423-1 (2023)

We thank Harrison et al.1 for their interest in our publication and for their comments but believe they have misquoted us and have misinterpreted our data. First, we did not suggest ‘that adamantanes, such as memantine or amantadine, … might have therapeutic use for COVID-19,’ as these authors state. This is a misrepresentation of our paper. Most importantly, our paper is not about memantine, which was simply used as a control, but rather about the more efficacious and potent compound, NMT5, an aminoadamantane nitrate that we show has efficacy in vivo in the Syrian golden hamster model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Please allow us to respond to their other points following the order of their paragraphs.

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Fig. 1: E viroporin protein channel recordings versus mock (empty vector)-transfected controls.
Fig. 2: E protein-mediated current is inhibited by HMA, as expected.

References

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Acknowledgements

This work was supported in part by National Institutes of Health grant nos. RF1 AG057409, R01 AG056259, R01 DA048882, R35 AG071734 and DP1 DA041722 (to S.A.L.), HOPE T32 Training Grant T32AI007384 (to L.N.C.), California Institute for Regenerative Medicine grant no. DISC2 COVID19-11811, and a COVID-19 award from Fast Grants (to S.A.L.).

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Authors and Affiliations

  1. Departments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, USA

    Chang-ki Oh, Juan Piña-Crespo, Maria Talantova, Lauren N. Carnevale & Stuart A. Lipton

  2. Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Charlotte Stoneham, Mary Lewinski & John Guatelli

  3. VA San Diego Healthcare System, San Diego, CA, USA

    Charlotte Stoneham, Mary Lewinski & John Guatelli

  4. Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA

    Stuart A. Lipton

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Contributions

C.-K.O., J.P.-C., M.T. and L.N.C. performed the biological experiments. C.S. and M.L. generated the E protein construct used here. S.A.L., C.-K.O. and J.G. discussed the findings. S.A.L. wrote the manuscript with revisions by all authors.

Corresponding author

Correspondence to Stuart A. Lipton.

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Competing interests

As in the original manuscript, the authors declare that S.A.L. is an inventor on patents for the use of memantine and various aminoadamantane nitrate compounds for neurodegenerative and neurodevelopmental disorders. He is also an inventor on composition of matter patents and use patents for aminoadamantane nitrate compounds in treating COVID-19 and other viral diseases. Per Harvard University guidelines, S.A.L. participates in a royalty-sharing agreement with his former institution, Boston Children’s Hospital/Harvard Medical School, which licensed the drug memantine (Namenda) to Forest Laboratories/Actavis/ Allergan/AbbVie for use in dementia. The aminoadamantane nitrate compounds are licensed to EuMentis Therapeutics, Inc. for both neurologic disease and COVID-19.

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Peer review information

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

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Oh, Ck., Piña-Crespo, J., Talantova, M. et al. Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nat Chem Biol 19, 1306–1308 (2023). https://doi.org/10.1038/s41589-023-01425-z

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