ArticleNature chemical biology2023
Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection.
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Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Proteome-wide profiling of S-nitrosylated proteins using the SNOTRAP probe and mass spectrometry-based detection.Nature protocols · 2026Review
- Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- Nitric Oxide at the Nexus of ACE2 Biology and COVID-19: Implications for Cardiovascular and Neurodegenerative Comorbidities.Physiological research · 2025Review
- Pathogenic Proteins Through the Lens of NMR Spectroscopy: Structural and Functional Insights into Disease.Cell biochemistry and biophysics · 2025Review
- FromActa pharmaceutica Sinica. B · 2025Article
- Sulfonohydrazide as a potential inhibitor of SARS-CoV-2 infection.Scientific reports · 2025Article
- Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nitric Oxide in the Treatment of COVID-19: Nasal Sprays, Inhalants and Nanoparticles.Biochemistry research international · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition.Antioxidants (Basel, Switzerland) · 2024Article
- Protein S-Nitrosylation: A Chemical Modification with Ubiquitous Biological Activities.The protein journal · 2024Review
- Predictive modeling for ubiquitin proteins through advanced machine learning technique.Heliyon · 2024Article
- Developing inhibitory peptides against SARS-CoV-2 envelope protein.PLoS biology · 2024Article
- A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding.Heliyon · 2024Article
- Endogenous currents in HEK 293 cells are inhibited by memantine.Nature chemical biology · 2023Article
- Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection.Nature chemical biology · 2023Article
- A regulatory role for the redox status of the pepino mosaic virus coat protein.PLoS pathogens · 2023Article
- Targeting SARS-CoV-2 and host cell receptor interactions.Antiviral research · 2023Review
- Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer's disease: Mechanistic insights and potential therapies.Frontiers in neural circuits · 2023Review
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Authors and funding
29 authors at 2 institutions in 1 country.
Chang-Ki OhDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-2489-4072
Tomohiro NakamuraDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Nathan BeutlerDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Xu ZhangDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Juan Piña-CrespoDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Maria TalantovaDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Swagata GhatakDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Dorit TrudlerDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Lauren N CarnevaleDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0451-0481
Scott R McKercherDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Malina A BakowskiCalibr, a division of the Scripps Research Institute, La Jolla, CA, USA.
Jolene K DiedrichDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.
Amanda J RobertsAnimal Models Core, Scripps Research Institute, La Jolla, CA, USA.
Ashley K WoodsCalibr, a division of the Scripps Research Institute, La Jolla, CA, USA.
Victor ChiCalibr, a division of the Scripps Research Institute, La Jolla, CA, USA.
Anil K GuptaCalibr, a division of the Scripps Research Institute, La Jolla, CA, USA.
Mia A RosenfeldDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8961-8231
Fiona L KearnsDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Lorenzo CasalinoDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3581-1148
Namir ShaabaniDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Hejun LiuDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-2412-7853
Ian A WilsonDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-6469-2419
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-9275-9553
Dennis R BurtonDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-6711-9864
John R YatesDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5267-1672
Cyrus BeckerEuMentis Therapeutics, Inc., Newton, MA, USA.ORCID http://orcid.org/0000-0001-7868-464X
Thomas F RogersDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Arnab K ChatterjeeCalibr, a division of the Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5171-7982
Stuart A LiptonDepartments of Molecular Medicine and Neuroscience, Neurodegeneration New Medicines Center, La Jolla, CA, USA. slipton@scripps.edu.ORCID http://orcid.org/0000-0002-3490-1259
Scripps Research Institute · USUniversity of California San Diego · US
Funding
Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6MTrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI DAVIS, TRISHA N. · 2012 to 2021
$20.7MStem Cells and AgingP20GM119943 · NIGMS · RHODE ISLAND HOSPITAL · PI QUESENBERRY, PETER J. · 2017 to 2021
$10.6MHOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7MNovel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0MLeadership in AD/ADRD Drug DiscoveryR35AG071734 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2021 to 2025
$5.4MTraining in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8MOmics Analyses of HIV and Substance Use DisorderR01DA048882 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI REPUNTE-CANONIGO, VEZ · 2019 to 2023
$4.3MDynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1MS-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3MNeuroprotective Mechanisms of S-Nitrosylated ApoE2 in Aging and Alzheimer's DiseaseR01AG061845 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI NAKAMURA, TOMOHIRO · 2018 to 2022
$2.4MIdentification and Verification of S-Nitrosylated Proteins in Bodily Fluids as Biomarkers for Parkinson's Disease and Lewy Body DementiaR61NS122098 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI NAKAMURA, TOMOHIRO · 2021 to 2021
$2.2MNIAID NIH HHS T32 AI007384NIAID NIH HHS UM1 AI144462NIA NIH HHS R01 AG056259NIA NIH HHS R01 AG061845NIA NIH HHS R35 AG071734NIA NIH HHS RF1 AG057409NIBIB NIH HHS T32 EB009380NIDA NIH HHS DP1 DA041722NIDA NIH HHS R01 DA048882NIGMS NIH HHS P20 GM119943NIGMS NIH HHS P41 GM103533NIGMS NIH HHS R01 GM132826NINDS NIH HHS R61 NS122098NINDS NIH HHS RF1 NS123298
Abstract
Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.
Indexed as
COVID-19Angiotensin-Converting Enzyme 2HumansPeptidyl-Dipeptidase AProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase ASpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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