Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines

Sadeghian, Issa; Heidari, Reza; Sadeghian, Sara; Raee, Mohammad Javad; Negahdaripour, Manica

doi:10.1016/j.ejps.2021.106094

Cited by 32 publications

(19 citation statements)

References 282 publications

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“…Cell penetrating peptides are gaining traction as therapeutics ( 53 ). The pJAK2 peptide we have tested may be useful as prophylactic as well as a therapeutic.…”

Section: Discussionmentioning

confidence: 99%

Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides

et al. 2022

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Suppressors of Cytokine Signaling (SOCS) are intracellular proteins that negatively regulate the induction of cytokines. Amongst these, SOCS1 and SOCS3 are particularly involved in inhibition of various interferons. Several viruses have hijacked this regulatory pathway: by inducing SOCS1and 3 early in infection, they suppress the host immune response. Within the cell, SOCS1/3 binds and inhibits tyrosine kinases, such as JAK2 and TYK2. We have developed a cell penetrating peptide from the activation loop of the tyrosine kinase, JAK2 (residues 1001-1013), denoted as pJAK2 that acts as a decoy and suppresses SOCS1 and 3 activity. This peptide thereby protects against several viruses in cell culture and mouse models. Herein, we show that treatment with pJAK2 inhibited the replication and release of the beta coronavirus HuCoV-OC43 and reduced production of the viral RNA, as measured by RT-qPCR, Western blot and by immunohistochemistry. We confirmed induction of SOCS1 and 3 in rhabdomyosarcoma (RD) cells, and this induction was suppressed by pJAK2 peptide. A peptide derived from the C-terminus of IFNα (IFNα-C) also inhibited replication of OC43. Furthermore, IFNα-C plus pJAK2 provided more potent inhibition than either peptide alone. To extend this study to a pandemic beta-coronavirus, we determined that treatment of cells with pJAK2 inhibited replication and release of SARS-CoV-2 in Calu-3 cells. We propose that these peptides offer a new approach to therapy against the rapidly evolving strains of beta-coronaviruses.

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“…Cell penetrating peptides are gaining traction as therapeutics ( 53 ). The pJAK2 peptide we have tested may be useful as prophylactic as well as a therapeutic.…”

Section: Discussionmentioning

confidence: 99%

Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides

et al. 2022

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“…However, some of these methods have shown drawbacks in high cytotoxicity and immunogenicity and low delivery yields for the transported bioactive molecules [13]. Consequently, non-viral delivery methods such as cell-penetrating peptides (CPPs) have gained significant attention due to their ease of synthesis and functionalization, low cytotoxicity, and immunogenicity [14,15].…”

Section: Introductionmentioning

confidence: 99%

Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2

et al. 2022

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At the beginning of 2020, the pandemic caused by the SARS-CoV-2 virus led to the fast sequencing of its genome to facilitate molecular engineering strategies to control the pathogen’s spread. The spike (S) glycoprotein has been identified as the leading therapeutic agent due to its role in localizing the ACE2 receptor in the host’s pulmonary cell membrane, binding, and eventually infecting the cells. Due to the difficulty of delivering bioactive molecules to the intracellular space, we hypothesized that the S protein could serve as a source of membrane translocating peptides. AHB-1, AHB-2, and AHB-3 peptides were identified and analyzed on a membrane model of DPPC (dipalmitoylphosphatidylcholine) using molecular dynamics (MD) simulations. An umbrella sampling approach was used to quantify the energy barrier necessary to cross the boundary (13.2 to 34.9 kcal/mol), and a flat-bottom pulling helped to gain a deeper understanding of the membrane’s permeation dynamics. Our studies revealed that the novel peptide AHB-1 exhibited comparable penetration potential of already known potent cell-penetrating peptides (CPPs) such as TP2, Buforin II, and Frenatin 2.3s. Results were confirmed by in vitro analysis of the peptides conjugated to chitosan nanoparticles, demonstrating its ability to reach the cytosol and escape endosomes, while maintaining high biocompatibility levels according to standardized assays.

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“…Improvement in the immunogenicity of DNA vaccines following CPP delivery was demonstrated against viral infections. Moreover, CPPs were incorporated into other delivery systems loaded with DNA vaccines especially nanoparticles to enhance their intracellular delivery ( Sadeghian et al, 2012 ). On the other hand, the potential of CPP/mRNA non-covalent complexation as delivery system was evaluated in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…Also, CPP-antigen conjugates can be internalized by APCs through endocytosis for presentation on the MHC-II molecules. Nucleic acids-based vaccines delivered by CPPs into the cells are translated to protein, and processed via the endogenous pathway ( Sadeghian et al, 2012 ; Backlund et al, 2022 ). In general, CPPs promoted the vehicle of protein-based antigens and NAs cargo in both in vitro and in vivo experiments.…”

Section: Introductionmentioning

confidence: 99%

Cell penetrating peptide: A potent delivery system in vaccine development

Hasannejad-Asl

Pooresmaeil²,

Takamoli³

et al. 2022

Front. Pharmacol.

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One of the main obstacles to most medication administrations (such as the vaccine constructs) is the cellular membrane’s inadequate permeability, which reduces their efficiency. Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are well-known as potent biological nanocarriers to overcome this natural barrier, and to deliver membrane-impermeable substances into cells. The physicochemical properties of CPPs, the attached cargo, concentration, and cell type substantially influence the internalization mechanism. Although the exact mechanism of cellular uptake and the following processing of CPPs are still uncertain; but however, they can facilitate intracellular transfer through both endocytic and non-endocytic pathways. Improved endosomal escape efficiency, selective cell targeting, and improved uptake, processing, and presentation of antigen by antigen-presenting cells (APCs) have been reported by CPPs. Different in vitro and in vivo investigations using CPP conjugates show their potential as therapeutic agents in various medical areas such as infectious and non-infectious disorders. Effective treatments for a variety of diseases may be provided by vaccines that can cooperatively stimulate T cell-mediated immunity (T helper cell activity or cytotoxic T cell function), and immunologic memory. Delivery of antigen epitopes to APCs, and generation of a potent immune response is essential for an efficacious vaccine that can be facilitated by CPPs. The current review describes the delivery of numerous vaccine components by various CPPs and their immunostimulatory properties.

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Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines

Cited by 32 publications

References 282 publications

Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides

Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides

Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2

Cell penetrating peptide: A potent delivery system in vaccine development

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