ArticleCell discovery2021
Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
What it found
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The trial behind it
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Structures of Nicotiana benthamiana importin-α1 complexes reveal mechanisms for plant virus NLS recognition.The Plant journal : for cell and molecular biology · 2026Article
- Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus.American journal of respiratory cell and molecular biology · 2025Article
- UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Resistance to SARS-CoV-2 infection in camelid nasal organoids is associated with lack of ACE2 expression.Npj viruses · 2024Article
- Association of specificFrontiers in immunology · 2024Article
- Article
- In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting.Nature communications · 2023Article
- HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells.Frontiers in cellular and infection microbiology · 2023Article
- Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy.Nature communications · 2022Article
- Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19.Epigenomes · 2022Review
- Article
- Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models.Journal of molecular liquids · 2021Article
- Author Correction: Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication.Cell discovery · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
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-α-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.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.