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27. Author Correction: Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication (Cell Discovery, (2021), 7, 1, (37), 10.1038/s41421-021-00279-w).

Author

Tu W.J., McCuaig R.D., Melino M., Rawle D.J., Le T.T., Yan K., Suhrbier A., Johnston R.L., Koufariotis L.T., Waddell N., Cross E.M., Tsimbalyuk S., Bain A., Ahern E., Collinson N., Phipps S., Forwood J.K., Seddiki N., Rao S., Tu W.J., McCuaig R.D., Melino M., Rawle D.J., Le T.T., Yan K., Suhrbier A., Johnston R.L., Koufariotis L.T., Waddell N., Cross E.M., Tsimbalyuk S., Bain A., Ahern E., Collinson N., Phipps S., Forwood J.K., Seddiki N., and Rao S.

Abstract

In the original publication of this Correspondence1, there is a missing affiliation for Dr. Nabila Seddiki. The corrected affiliations for Dr. Nabila Seddiki should be as follows: 9U955, Equipe 16, Creteil, France. 10Universite Paris-Est Creteil, Faculte de medecine, Creteil, France. 11Vaccine Research Institute (VRI), Creteil, France, 12INSERM U1184, CEA, IDMIT Department, Immunology of Viral, Auto- Immune, Hematological and Bacterial Diseases (IMVA-HB), Universite Paris-Saclay, 92265 Fontenay-aux-Roses, France. This correction does not affect the description of the results or the conclusion of this work. In the original publication of this Correspondence1, there was a mistake in Fig. 2o. There was a mathematical error in the subtraction of background for the TCID50 assay. We have now corrected the error in background subtraction and have replotted the graph. We have engaged an independent statistician to validate the updated graph. This correction does not alter the overall results or the conclusions of this work. (Figure presented.).Copyright © The Author(s) 2021

Published
2021

28. Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication.

Author

Tu W.J., McCuaig R.D., Melino M., Rawle D.J., Le T.T., Yan K., Suhrbier A., Johnston R.L., Koufariotis L.T., Waddell N., Cross E.M., Tsimbalyuk S., Bain A., Ahern E., Collinson N., Phipps S., Forwood J.K., Seddiki N., Rao S., Tu W.J., McCuaig R.D., Melino M., Rawle D.J., Le T.T., Yan K., Suhrbier A., Johnston R.L., Koufariotis L.T., Waddell N., Cross E.M., Tsimbalyuk S., Bain A., Ahern E., Collinson N., Phipps S., Forwood J.K., Seddiki N., and Rao S.

Abstract

Treatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription. LSD1 colocalized with ACE2 at the cell surface to maintain demethylated SARS-CoV-2 spike receptor-binding domain lysine 31 to promote virus-ACE2 interactions. Two newly developed peptide inhibitors competitively inhibited virus-ACE2 interactions, and demethylase access to significantly inhibit viral replication. Similar to some other predominantly plasma membrane proteins, ACE2 had a novel nuclear function: its cytoplasmic domain harbors a nuclear shuttling domain, which when demethylated by LSD1 promoted importin-alpha-dependent nuclear ACE2 entry following infection to regulate active transcription. A novel, cell permeable ACE2 peptide inhibitor prevented ACE2 nuclear entry, significantly inhibiting viral replication in SARS-CoV-2-infected cell lines, outperforming other LSD1 inhibitors. These data raise the prospect of post-exposure prophylaxis for SARS-CoV-2, either through repurposed LSD1 inhibitors or new, nuclear-specific ACE2 inhibitors.Copyright © 2021, The Author(s).

Published
2021

45. Crystal structure of Importin alpha 2 in complex with LSD1 NLS

Author

Tu, W.J., primary, McGuaig, R., additional, Tan, H.Y.A., additional, Hardy, C., additional, Seddiki, N., additional, Ali, S., additional, Dahlstrom, J.E., additional, Bean, E.G., additional, Dunn, J., additional, Forwood, J.K., additional, Tsimbalyuk, S., additional, Smith, K.M., additional, Yip, D., additional, Malik, L., additional, Prasana, T., additional, Milburn, P., additional, and Rao, S., additional

Published
2020
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46. Crystal structure of Importin Alpha 3 in complex with human LSD1 NLS

Author

Tu, W.J., primary, McCuaig, R., additional, Tan, H.Y.A., additional, Hardy, K., additional, Seddiki, N., additional, Ali, S., additional, Dahlstrom, J.E., additional, Bean, E.G., additional, Dunn, J., additional, Forwood, J.K., additional, Tsimbalyuk, S., additional, Smith, K., additional, Yip, D., additional, Malik, L., additional, Prasana, T., additional, Milburn, P., additional, and Rao, S., additional

Published
2020
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47. Crystal structure of Importin alpha 2 in complex with LSD1 NLS S111E mutant

Author

Tu, W.J., primary, McCuaig, R., additional, Tan, A.H.Y., additional, Hardy, K., additional, Seddiki, N., additional, Ali, S., additional, Dahlstron, J.E., additional, Bean, E.G., additional, Dunn, J., additional, Forwood, J.K., additional, Tsimbalyuk, S., additional, Smith, K.M., additional, Yip, D., additional, Malik, L., additional, Prasana, T., additional, Milburn, P., additional, and Rao, S., additional

Published
2020
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