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Computational Design of Potent D-Peptide Inhibitors of SARS-CoV-2.
Valiente, Pedro A; Wen, Han; Nim, Satra; Lee, JinAh; Kim, Hyeon Ju; Kim, Jinhee; Perez-Riba, Albert; Paudel, Yagya Prasad; Hwang, Insu; Kim, Kyun-Do; Kim, Seungtaek; Kim, Philip M.
  • Valiente PA; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Wen H; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Nim S; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Lee J; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Kim HJ; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Kim J; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Perez-Riba A; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Paudel YP; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
  • Hwang I; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • Kim KD; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • Kim S; Zoonotic Virus Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • Kim PM; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
J Med Chem ; 64(20): 14955-14967, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1461960
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / SARS-CoV-2 Topics: Variants Limits: Animals Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2021 Document Type: Article Affiliation country: Acs.jmedchem.1c00655

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptides / SARS-CoV-2 Topics: Variants Limits: Animals Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2021 Document Type: Article Affiliation country: Acs.jmedchem.1c00655