Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein(84 views) Sadremomtaz A, Al-dahmani ZM, Ruiz-moreno AJ, Monti A, Wang C, Azad T, Bell JC, Doti N, Velasco-velázquez MA, De Jong D, De Jonge J, Smit J, Dömling A, Van Goor H, Groves MR
XB20 Drug Design, Groningen Research Institute of Pharmacy, University of Groningen, 9700 AD Groningen, The Netherlands.
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands.
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico (UNAM), Ciudad de Mexico 04510, Mexico.
Unidad Periférica de Investigación en Biomedicina Translacional, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Félix Cuevas 540, Ciudad de Mexico 03229, Mexico.
Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de Mexico 04510, Mexico.
Institute of Biostructures and Bioimaging (IBB)-CNR, Via Mezzocannone, 16, 80134 Napoli, Italy.
Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, K1H 8L6 ON, Canada.
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5 ON, Canada.
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3720BA Bilthoven, The Netherlands.
References: Not available.
Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein
The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the viral genome. Therefore, antagonists of this interaction could allow a modality for therapeutic intervention. Peptides can inhibit the S-RBD:ACE2 interaction by interacting with the protein-protein interface. In this study, protein contact atlas data and molecular dynamics simulations were used to locate interaction hotspots on the secondary structure elements α1, α2, α3, β3, and β4 of ACE2. We designed a library of discontinuous peptides based upon a combination of the hotspot interactions, which were synthesized and screened in a bioluminescence-based assay. The peptides demonstrated high efficacy in antagonizing the SARS-CoV-2 S-RBD:ACE2 interaction and were validated by microscale thermophoresis which demonstrated strong binding affinity (∼10 nM) of these peptides to S-RBD. We anticipate that such discontinuous peptides may hold the potential for an efficient therapeutic treatment for COVID-19.
Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(562 views) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 ViewExport to BibTeXExport to EndNote