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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/4531| The first-in-class peptide binder to the SARS-CoV-2 spike protein | |
| Genwei Zhang. Sebastian Pomplun. Alexander Robert Loftis. Andrei Loas. Bradley L. Pentelute. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.03.19.999318 | |
| Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 200,000 confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved ACE2 and SARS-CoV-2-RBD co-crystal structure, we observed that the ACE2 peptidase domain (PD) 1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD 1 helix composed entirely of proteinogenic amino acids. Chemical synthesis of this human derived sequence was complete in 1.5 hours and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry revealed that this peptide specifically associates with the SARS-CoV-2-RBD with low nanomolar affinity. This peptide binder to SARS-CoV-2-RBD provides new avenues for COVID-19 treatment and diagnostic modalities by blocking the SARS-CoV-2 spike protein interaction with ACE2 and thus precluding virus entry into human cells. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/10.1101/2020.03.19.999318v1.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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