scholarly journals MicroRNA‑28‑3p inhibits angiotensin‑converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17

2021 ◽  
Vol 48 (4) ◽  
Author(s):  
Yun Xu ◽  
Yi Li
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Spike Protein ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
A Disintegrin And Metalloproteinase

scholarly journals SARS-CoV-2 Inhibition by Sulfonated Compounds

2020 ◽  
Vol 8 (12) ◽  
pp. 1894
Author(s):  
Matteo Gasbarri ◽  
Philip V’kovski ◽  
Giulia Torriani ◽  
Volker Thiel ◽  
Francesco Stellacci ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Vesicular Stomatitis Virus ◽  
Inhibitory Activity ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Virucidal Activity ◽  
Angiotensin Converting Enzyme 2 ◽  
Vesicular Stomatitis ◽  
Heparan Sulfates

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible.

scholarly journals Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2

2020 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xuanxuan Li ◽  
Xiao-dong Su ◽  
Haiguang Liu
Keyword(s):  
Molecular Dynamics ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Computational Analysis ◽  
Spike Protein ◽  
Short Peptides ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

scholarly journals Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis

2020 ◽  
Author(s):  
Mythily Srinivasan ◽  
Susan L Zunt ◽  
Lawrence I Goldblatt
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Symptoms ◽  
Cell Entry ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Immunofluorescence Analysis ◽  
Angiotensin Converting Enzyme 2 ◽  
Diagnosis And Prognosis ◽  
Oral Epithelial

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses the angiotensin converting enzyme (ACE)-2 as the host receptor for target cell entry. The extent and distribution of ACE-2 has been associated with the clinical symptoms of coronavirus disease (COVID)-19. Here we show by immunofluorescence analysis that the ACE2 is abundantly expressed in oral mucosa, particularly in the surface epithelial cells suggesting that these cells could represent sites of entry for SARS-CoV-2. Further, together with the reports on ACE2 ectodomain shedding, we discuss the rationale for the hypothesis that the ACE-2 measurement in saliva could be a marker for COVID-19 infection during early phase following SARS-CoV-2 exposure.

scholarly journals Dinamika Interaksi Reseptor ACE2 dan SARS-CoV-2 Terhadap Manifestasi Klinis COVID-19

2020 ◽  
Vol 1 (2) ◽  
pp. 70-76
Author(s):  
Risma Ikawaty
Keyword(s):  
Systematic Review ◽  
Genetic Variation ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Manifestation ◽  
Meta Analysis ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Extra Pulmonary

Abstract— Background: A human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be responsible for coronavirus disease 2019 (COVID-19). Pulmonary complications has been considered as the classical clinical manifestations until symptoms on the extra-pulmonary organs may also occur recently, which might be linked to the presence of angiotensin-converting enzyme 2 (ACE2) receptor. Objective: This article evaluates clinical manifestation of COVID-19 and the presence of ACE2 receptor by looking at its interaction to SARS-CoV-2. Methods: 27 articles in English have been selected through search engine PubMed and Google Scholar by using specific keywords. These articles include research journals, case report, systematic review and meta-analysis, and textbooks. Result: Pathogenesis of COVID-19 begins with the binding of spike protein SARS-CoV-2 to ACE2 receptor of host cells. Clinical manifestation of COVID-19 is no longer limited to the pulmonary system but also extra-pulmonary systems since ACE2 receptor abundantly distributed on the other organs. Further, genetic variations of region binding protein of viral spike protein and ACE2 receptor may predispose clinical manifestation of COVID19.  Conclusions: Dynamic interplay between SARS-CoV-2 and receptor ACE2 has great implication to the clinical symptoms. Genetic variation of spike protein SARS-CoV-2 play role not only for cross transmission but also its virulence, while genetic variation of human receptor ACE2 influences its susceptibility or resistance against the infection. Keywords: ACE2 receptor, Coronavirus Diseases-19, clinical manifestation, SARS-CoV-2, genetic variation. Abstrak— Virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) merupakan penyebab utama dari coronavirus disease 2019 (COVID-19). Komplikasi pernapasan diangap sebagai gejala klinis klasik hingga akhirnya timbul berbagai manifestasi klinis di organ lain sebagai gejala awal COVID19. Hal ini kemudian dihubungkan dengan reseptor angiotensin-converting enzyme 2 (ACE2). Artikel ini mengevaluasi manifestasi klinis yang disebabkan  interaksi antara reseptor ACE2 dan SARS-CoV-2. PubMed dan Google Scholar digunakan untuk mencari artikel dengan kata kunci yang spesifik untuk COVID-19, SARS-CoV-2, reseptor ACE2, variasi genetik, dan manifestasi klinisnya. Dua puluh tujuh artikel berbahasa Inggris yang digunakan termasuk jurnal penelitian, laporan kasus, systematic review, meta-analysis, dan buku teks. Patogenesis COVID19 dimulai dengan ikatan protein Spike SARS-CoV-2 dan reseptor ACE2. Studi memperlihatkan bahwa reseptor ACE2 ditemui di berbagai jaringan/organ selain organ sistem respirasi sehingga memperlihatkan gejala klinis yang berbeda. Selain itu variasi genetik yang terdapat pada protein spike dari virus dan reseptor ACE2 juga merupakan faktor penting pada terjadinya COVID19. Penulis menyimpulkanbahwa dinamika interaksi antara reseptor ACE2 dan protein spike SARS-CoV-2 termasuk variasi genetic, keduanya memegang peranan penting terhadap suseptibilitas/resistensi dan manifestasi klinis COVID19. Kata kunci: Coronavirus Diseases-19, manifestasi klinis,  reseptor ACE2, SARS-CoV-2, variasi genetik.

scholarly journals Transferrin receptor is another receptor for SARS-CoV-2 entry

2020 ◽  
Author(s):  
Xiaopeng Tang ◽  
Mengli Yang ◽  
Zilei Duan ◽  
Zhiyi Liao ◽  
Lei Liu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Angiotensin Converting Enzyme ◽  
Transferrin Receptor ◽  
Cell Membranes ◽  
Virus Entry ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractAngiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

scholarly journals Transferrin receptor is another receptor for SARS-CoV-2 entry

2020 ◽  
Author(s):  
Ren Lai ◽  
Xiaopeng Tang ◽  
Mengli Yang ◽  
Zilei Duan ◽  
Zhiyi Liao ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Angiotensin Converting Enzyme ◽  
Transferrin Receptor ◽  
Cell Membranes ◽  
Virus Entry ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ∼16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

Sign in / Sign up

Export Citation Format

Share Document