Cell-Penetrating Peptides for Antiviral Drug Development
Abstract
:1. Nature and Scope of the Challenges Presented by Viral Infections
2. The Advent of Cell-Penetrating Peptides
Antiviral cargo | Targeted virus | Conjugated CPP | Experimental systems | Limitations – CPP composition requirements |
---|---|---|---|---|
PMO | RNA viruses | |||
West Nile virus [66,67] | (RXR)4XB | Cell culture | Dose-dependent toxicity in cell culture and mice | |
Mouse | ||||
Japanese encephalitis virus [67] | (RXR)4XB | Cell culture | ||
St. Louis encephalitis virus [67] | (RXR)4XB | Cell culture | ||
Dengue virus [68,69,70] | (RXR)4XB | Cell culture | ||
R5F2R4C | Mouse | |||
R9F2C | ||||
SARS coronavirus [71] | R9F2C | Cell culture | ||
R5F2R4C | ||||
Mouse hepatitis virus [59,63] | R9F2C (RXR)4XB | Cell culture Mouse | PPMO toxicity in mice when treatment given after MHV challenge | |
PPMO with higher number of arginine residues exhibit greater antiviral activity in cell culture | ||||
PPMO with insertions of 6-aminohexanoic acid offer greater protection in mouse | ||||
Equine arteritis virus [72] | R9F2C | Cell culture | ||
Porcine reproductive and respiratory syndrome virus [73] | R5F2R4C | Cell culture | ||
Poliovirus 1 [75] | R9F2C | Cell culture | in vitro toxicity when longer periods of treatment | |
(RXR)4XB | Mouse | |||
Human rhinovirus 14 | R9F2C | Cell culture | ||
[75] | (RXR)4XB | |||
Coxsackievirus B2 | R9F2C | Cell culture | ||
[75] | (RXR)4XB | |||
Coxsackievirus B3 | (RXR)4XB | Cell culture | ||
[76] | Mouse | |||
Foot-and-mouth disease virus [74] | R9F2C | Cell culture | ||
Sindbis virus [77] | R9F2C | Cell culture | ||
Venezuelan equine encephalitis virus [77] | (RXR)4XB | Cell culture | ||
Mouse | ||||
Ebola virus [64,78] | (RXR)4XB | Cell culture Mouse | PPMO with insertions of 6-aminohexanoic acid and higher number of arginine-6-aminohexanoic repeats offer greater protection in mouse | |
R9F2C | ||||
(RX)n=2-8B | ||||
(RB)8B | ||||
Respiratory syncytial virus [79] | (RXR)4XB | Cell culture | Endosomal entrapment | |
Mouse | ||||
Measles virus [80] | (RXR)4XB | Cell culture | ||
Influenza A virus [81,82,83] | (RXR)4XB | Cell culture | Higher doses of PPMO induced abnormal infiltration of mouse lungs by immune system cells | |
R5F2R4C | Mouse | |||
DNA viruses | ||||
Kaposi’s sarcoma-associated herpesvirus [84,85] | R5F2R4C | Cell culture | ||
(RXR)4XB | ||||
Herpesvirus type 1 | (RXR)4XB | Cell culture | ||
[86] | Mouse | |||
PNA | HIV-1 [91,92,93,94,95,99,100,101] | Disulfide-linked: | Cell culture Some preliminary mouse studies for tat and penetratin conjugates | Endosomal entrapment requiring lysosomotropic agents Nature of CPP and of CPP-PNA linkage had an effect on conjugate activity |
tat | ||||
penetratin | ||||
transportan | ||||
transportan 21 | ||||
transportan 22 | ||||
R6-penetratin | ||||
Stably-linked: | ||||
tat | ||||
transportan | ||||
transportan 21 | ||||
Japanese encephalitis virus [96] | tat | Cell culture | ||
siRNA | Hepatitis C virus [102] | tat | Cell culture | |
HIV-1 [15] | nonamer arginine (9R) | Mouse | ||
non-covalent binding | ||||
Proteins | HIV-1 [103,104,105] | tat | Cell culture | |
Human papillomavirus type 18 [106] | 9R | Cell culture | Nature of CPP directly impacted the level of antiviral activity | |
PTD4 |
3. Delivery of Antisense Agents
3.1. Delivery of Phosphorodiamidate Morpholino Oligomers (PMOs)
3.1.1. Nature of Peptides Conjugated to PMOs
3.1.2. PPMOs against RNA Viruses
3.1.3. PPMOs against DNA Viruses
3.1.4. Enhancement of PMO Antisense Activity
3.1.5. PPMO Toxicity
3.2. Delivery of Peptide-Nucleic Acids (PNAs)
3.2.2. Preclinical Studies of CPP-PNA Conjugates in Mice
3.3. Delivery of Small Interfering RNAs (siRNAs)
6. Conclusions
References
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Delcroix, M.; Riley, L.W. Cell-Penetrating Peptides for Antiviral Drug Development. Pharmaceuticals 2010, 3, 448-470. https://doi.org/10.3390/ph3030448
Delcroix M, Riley LW. Cell-Penetrating Peptides for Antiviral Drug Development. Pharmaceuticals. 2010; 3(3):448-470. https://doi.org/10.3390/ph3030448
Chicago/Turabian StyleDelcroix, Melaine, and Lee W. Riley. 2010. "Cell-Penetrating Peptides for Antiviral Drug Development" Pharmaceuticals 3, no. 3: 448-470. https://doi.org/10.3390/ph3030448