Computational Design of Potent D-Peptide Inhibitors of SARS-CoV-2
Autor: | Seungtaek Kim, Hyeon Ju Kim, Jinhee Kim, Yagya Prasad Paudel, Satra Nim, Pedro A. Valiente, Kyun-Do Kim, JinAh Lee, Albert Perez-Riba, Philip M. Kim, Han Wen, Insu Hwang |
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Rok vydání: | 2021 |
Předmět: |
Protein Data Bank (RCSB PDB)
Peptide Pharmacology 01 natural sciences Article Virus 03 medical and health sciences Chlorocebus aethiops Drug Discovery Animals Potency Vero Cells 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology SARS-CoV-2 010405 organic chemistry Chemistry Immunogenicity In vitro 3. Good health 0104 chemical sciences Molecular Docking Simulation biology.protein Vero cell Molecular Medicine Antibody Peptides |
Zdroj: | Journal of Medicinal Chemistry |
ISSN: | 1520-4804 0022-2623 |
Popis: | Blocking the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) is an attractive therapeutic approach to prevent the virus from entering human cells. While antibodies and other modalities have been developed to this end, d-amino acid peptides offer unique advantages, including serum stability, low immunogenicity, and low cost of production. Here, we designed potent novel D-peptide inhibitors that mimic the ACE2 α1-binding helix by searching a mirror-image version of the PDB. The two best designs bound the RBD with affinities of 29 and 31 nM and blocked the infection of Vero cells by SARS-CoV-2 with IC50 values of 5.76 and 6.56 μM, respectively. Notably, both D-peptides neutralized with a similar potency the infection of two variants of concern: B.1.1.7 and B.1.351 in vitro. These potent D-peptide inhibitors are promising lead candidates for developing SARS-CoV-2 prophylactic or therapeutic treatments. |
Databáze: | OpenAIRE |
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