ArticleLife sciences2020
Structural analysis of ACE2 variant N720D demonstrates a higher binding affinity to TMPRSS2.
Article in Life sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Rationale for combined therapies in severe-to-critical COVID-19 patients.Frontiers in immunology · 2023Review
- Review
- Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS-CoV-2 from 946 whole-exome sequencing data in the Turkish population.Journal of medical virology · 2022Article
- Characterization of ACE2 naturally occurring missense variants: impact on subcellular localization and trafficking.Human genomics · 2022Article
- Discovery of natural products to block SARS-CoV-2 S-protein interaction with Neuropilin-1 receptor: A molecular dynamics simulation approach.Microbial pathogenesis · 2022Article
- Screening of potential spike glycoprotein / ACE2 dual antagonists against COVID-19 in silico molecular docking.Journal of virological methods · 2022Article
- SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET.Cell chemical biology · 2022Article
- The Complexity of SARS-CoV-2 Infection and the COVID-19 Pandemic.Frontiers in microbiology · 2022Review
- SARS-CoV-2 Susceptibility andFrontiers in genetics · 2022Article
- Structural modelling of SARS-CoV-2 alpha variant (B.1.1.7) suggests enhanced furin binding and infectivity.Virus research · 2021Article
- Perturbation of ACE2 Structural Ensembles by SARS-CoV-2 Spike Protein Binding.Journal of chemical theory and computation · 2021Article
- Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection.Archives of virology · 2021Review
- Natural products provide a new perspective for anti-complement treatment of severe COVID-19: a review.Chinese medicine · 2021Review
- Remdesivir MD Simulations Suggest a More Favourable Binding to SARS-CoV-2 RNA Dependent RNA Polymerase Mutant P323L Than Wild-Type.Biomolecules · 2021Article
- Genetic and epigenetic factors associated with increased severity of Covid-19.Cell biology international · 2021Review
- Theoretical Evaluation of Novel Thermolysin Inhibitors fromMolecules (Basel, Switzerland) · 2021Article
- Cellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches.ImmunoTargets and therapy · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel member of the betacoronaviruses family affecting the lower respiratory tract mainly through binding to angiotensin converting enzyme 2 (ACE2) via its S-protein. Genetic analysis of (ACE2) gene revealed several variants that have been suggested to regulate the interaction with S protein. This study investigates the N720D variant, positioned in the collectrin-like domain (CLD) at proximity to type II transmembrane serine protease (TMPRSS2) cleavage site. MAIN
methodsThe effect of N720D variant on ACE2 structure and thermodynamic stability was studied by DynaMut. HDOCK was utilised to model TMPRSS2 protease binding to ACE2 WT and D720 variant cleavage site. PRODIGY was used to calculate binding affinities and MD simulation tools calculated the at 100 ns for ACE2 apo structure and the ACE2-TMPRSS2 complex. KEY
findingsThe N720D variant is a more dynamic structure with a free energy change (ΔΔG): -0.470 kcal/mol. As such, introducing a tighter binding affinity of K SIGNIFICANCE: The hotspot N720D variant in the CLD of ACE2 affected the stability and flexibility of ACE2 by increasing the level of motion in the loop region, resulting in a more favourable site for TMPRSS2 binding and cleavage. Consequently, this would facilitate S-protein binding and can potentially increase viral entry highlighting the importance of variants affecting the ACE2-TMPRSS2 complex.
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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.