An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants
| العنوان: | An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants |
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| المؤلفون: | Marcos Gonzalez, Kayvan Niazi, Oleksandr Buzko, Wendy Higashide, Ashley Richardson, Shiho Tanaka, Gard Nelson, Shahrooz Rabizadeh, Sofija Buta, Justin Taft, Roosheel S. Patel, Annie Shin, Patrick Soon-Shiong, C. Anders Olson, Patricia Spilman, Dusan Bogunovic |
| المصدر: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Science, Biophysics, Molecular Dynamics Simulation, medicine.disease_cause, Antiviral Agents, Article, Virus, Protein Domains, medicine, Humans, Amino Acid Sequence, skin and connective tissue diseases, Peptide sequence, Mutation, Multidisciplinary, Drug discovery, SARS-CoV-2, Chemistry, Wild type, COVID-19, Virus Internalization, Fusion protein, Virology, In vitro, Amino Acid Substitution, Spike Glycoprotein, Coronavirus, Medicine, Angiotensin-Converting Enzyme 2, Decoy, hormones, hormone substitutes, and hormone antagonists, Protein Binding, Signal Transduction |
| الوصف: | The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might increase its affinity for S RBD and screened candidate ACE2 decoys in vitro. The lead ACE2(T27Y/H34A)-IgG1FC fusion protein with enhanced S RBD affinity shows greater live SARS-CoV-2 virus neutralization capability than wild type ACE2. MD simulation was used to predict the effects of S RBD variant mutations on decoy affinity that was then confirmed by testing of an ACE2 Triple Decoy that included an additional enzyme activity-deactivating H374N substitution against mutated S RBD. The ACE2 Triple Decoy maintains high affinity for mutated S RBD, displays enhanced affinity for S RBD N501Y or L452R, and has the highest affinity for S RBD with both E484K and N501Y mutations, making it a viable therapeutic option for the prevention or treatment of SARS-CoV-2 infection with a high likelihood of efficacy against variants. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06dcca5a3e11ccd11c6c21b298afe576 https://doi.org/10.1038/s41598-021-91809-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....06dcca5a3e11ccd11c6c21b298afe576 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20452322 |
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