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 is hence 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.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviation used
- 3CLpro
- C30 Endopeptidase/3C-like protease
- SARS-CoV-2
- severe acute respiratory syndrome-coronavirus-2
- COVID-19
- Coronavirus Disease-2019
- Cro
- Crotamine
- L-CDP
- crotamine derivative L-enantiomeric peptide
- D-CDP
- crotamine derivative D-enantiomeric peptide
- WHO
- World Health Organization
- NSP
- Nonstructural proteins
- AMP
- Antimicrobial peptides
- ZIKV
- Zika virus
- DENV
- Dengue virus
- IAV
- Influenza A virus
- CPP
- Cell-penetrating polypeptide
- SPR
- Surface plasmon resonance
- KD
- Dissociation constant
- HIV-1
- Human immunodeficiency virus 1
- RCC
- Redox cycling compound
- TCEP
- Tris(2-carboxyethyl)phosphine hydrochloride
- MIC
- Minimum Inhibitory Concentration
- dpi
- Days post-infection
- RMSD
- Root-mean-square deviation
- RMSF
- Root-mean-square flutuation
- RoG
- Radius of gyration
- MD
- Molecular dynamics
- CEVAP
- Center for the Study of Venoms and Venomous Animals
- HRP-PR
- Horseradish peroxidase-phenol red
- RT
- Room temperature
- MST
- Microscale thermophoresis
- PBS
- Phosphate buffered saline
- MTT
- 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- FCS
- Fetal calf serum
- DMEM
- Dulbecco′s Modified Eagle′s Medium
- MOI
- Multiplicity of infection
- NVT
- Number, volume, and temperature
- NPT
- Number, pressure, and temperature.
