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Design of D-Amino Acids SARS-CoV-2 Main Protease Inhibitors Using the Cationic Peptide from Rattlesnake Venom as a Scaffold.
Eberle, Raphael J; Gering, Ian; Tusche, Markus; Ostermann, Philipp N; Müller, Lisa; Adams, Ortwin; Schaal, Heiner; Olivier, Danilo S; Amaral, Marcos S; Arni, Raghuvir K; Willbold, Dieter; Coronado, Mônika A.
  • Eberle RJ; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Gering I; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße, 40225 Düsseldorf, Germany.
  • Tusche M; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Ostermann PN; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Müller L; Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
  • Adams O; Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
  • Schaal H; Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
  • Olivier DS; Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
  • Amaral MS; Integrated Sciences Center, Campus Cimba, Federal University of Tocantins, Araguaína 77824-838, TO, Brazil.
  • Arni RK; Institute of Physics, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil.
  • Willbold D; Multiuser Center for Biomolecular Innovation, Department of Physics, IBILCE, Universidade Estadual Paulista (UNESP), São José do Rio Preto 15054-000, SP, Brazil.
  • Coronado MA; Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.
Pharmaceuticals (Basel) ; 15(5)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1810078
ABSTRACT
The C30 endopeptidase (3C-like protease; 3CLpro) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and, hence, is a promising drug target. Molecules isolated from animals, insects, plants, or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus, has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial, and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low µM range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo, probably targeting the viral protease 3CLpro.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2022 Document Type: Article Affiliation country: Ph15050540

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2022 Document Type: Article Affiliation country: Ph15050540