Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19
| العنوان: | Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19 |
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| المؤلفون: | Jacques Fantini, Nouara Yahi, Henri Chahinian |
| المساهمون: | Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Debanne, Dominique |
| المصدر: | Biochemical and Biophysical Research Communications Biochemical and Biophysical Research Communications, 2020, 538, pp.132-136. ⟨10.1016/j.bbrc.2020.10.015⟩ Biochemical and Biophysical Research Communications, Elsevier, 2020, 538, pp.132-136. ⟨10.1016/j.bbrc.2020.10.015⟩ |
| بيانات النشر: | Elsevier Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, [SDV]Life Sciences [q-bio], Plasma protein binding, Azithromycin, medicine.disease_cause, Coronavirus Vaccine SARS-CoV-2 Ganglioside Azithromycin Hydroxychloroquine Lipid raft ACE-2, Biochemistry, Epitope, RBD, 0302 clinical medicine, Gangliosides, Neutralizing antibody, Lipid raft, Coronavirus, receptor binding domain, biology, Chemistry, SARS-CoV, 3. Good health, [SDV] Life Sciences [q-bio], NTD, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, SARS-coronavirus-2, ACE-2, angiotensin converting enzyme-2, Angiotensin-Converting Enzyme 2, COVID-19, coronavirus disease 19, Hydroxychloroquine, COVID-19 Vaccines, N-terminal domain, SARS-CoV, severe acute respiratory syndrome coronavirus, Biophysics, SARS-CoV-2, SARS-coronavirus-2, Article, 03 medical and health sciences, RBD, receptor binding domain, Protein Domains, Ganglioside binding, medicine, Humans, NTD, N-terminal domain, Binding site, coronavirus disease 19, Molecular Biology, severe acute respiratory syndrome coronavirus, Ganglioside, Binding Sites, SARS-CoV-2, COVID-19, Cell Biology, Virology, Antibodies, Neutralizing, angiotensin converting enzyme-2, 030104 developmental biology, biology.protein, Vaccine |
| الوصف: | Covid-19 is an infectious respiratory disease due to a coronavirus named SARS-CoV-2. A critical step of the infection cycle is the binding of the virus spike S protein to the cellular ACE-2 receptor. This interaction involves a receptor binding domain (RBD) located at the center of the S trimer, whereas the lateral N-terminal domain (NTD) displays a flat ganglioside binding site that enables the virus to bind to lipid rafts of the plasma membrane, where the ACE-2 receptor resides. S protein binding to lipid rafts can be blocked by hydroxychloroquine, which binds to gangliosides, and by azithromycin, which binds to the NTD. Based on these data, we identified the NTD of SARS-CoV-2 as a promising target for both therapeutic and vaccine strategies, a notion later supported by the discovery, in convalescent Covid-19 patients, of a neutralizing antibody (4A8) that selectively binds to the NTD. The 4A8 epitope overlaps the ganglioside binding domain, denying any access of the virus to lipid rafts when the antibody is bound to the S protein. Thus, our data explain why antibody binding to the tip of the NTD results in SARS-CoV-2 neutralization. The high level of conservation of the ganglioside binding domain of SARS-CoV-2 (100% identity in 584 of 600 isolates analyzed worldwide) offers unique opportunities for innovative vaccine/therapeutic strategies. Highlights • Gangliosides in lipid rafts play a key role in SARS-CoV-2 infection. • The N-terminal domain (NTD) of the virus spike protein binds to gangliosides. • Hydroxychloroquine and azithromycin prevent NTD-gangliosides interactions. • Neutralizing antibodies isolated from Covid-19 patients are directed against the NTD. • The NTD is a promising target for therapeutic and vaccine strategies against Covid-19. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1090-2104 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.10.015⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25615fc971e306afee38dbce726634e6 http://europepmc.org/articles/PMC7547605 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....25615fc971e306afee38dbce726634e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10902104 0006291X |
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| DOI: | 10.1016/j.bbrc.2020.10.015⟩ |