We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion. We propose the use of different nanosized carriers, formed by several carbosilane dendritic wedges to deliver two different peptides designed to inhibit host interaction or virus entry. The antiviral activity of the peptide-dendrimers, as well as of free peptides and free dendrimers was evaluated through the use of SARS-CoV-2 pseudotyped lentivirus. The results obtained show that peptides designed to block host-pathogen interaction represent a valuable strategy for viral inhibition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijpharm.2024.124389 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targetable domains for the design of peptide-dendrimer inhibitors of SARS-CoV-2.
Int J Pharm
August 2024
Department of Agricultural Science, University of Naples 'Federico II', Via Università 100, Portici, 80055 Portici, Italy. Electronic address:
We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion.
View Article and Find Full Text PDFSARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection.
Pharmaceutics
December 2023
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs.
View Article and Find Full Text PDFUncoupling the BMP receptor antagonist function from the WNT agonist function of R-spondin 2 using the inhibitory peptide dendrimer RW.
J Biol Chem
February 2022
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Institute of Molecular Biology (IMB), Mainz, Germany. Electronic address:
Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMP receptor type 1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the thrombospondin 1 domain of RSPO2, which specifically prevents binding between RSPO2 and BMP receptor type 1A without altering WNT signaling.
View Article and Find Full Text PDFAn Immunomodulatory Peptide Dendrimer Inspired from Glatiramer Acetate.
Angew Chem Int Ed Engl
December 2021
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
Glatiramer acetate (GA) is a random polypeptide drug used to treat multiple sclerosis (MS), a chronic autoimmune disease. With the aim of identifying a precisely defined alternative to GA, we synthesized a library of peptide dendrimers with an amino acid composition similar to GA. We then challenged the dendrimers to trigger the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) from human monocytes, which is one of the effects of GA on immune cells.
View Article and Find Full Text PDFNanoparticle Conjugation Stabilizes and Multimerizes β-Hairpin Peptides To Effectively Target PD-1/PD-L1 β-Sheet-Rich Interfaces.
J Am Chem Soc
January 2020
Yonsei Frontier Lab, Department of Pharmacy , Yonsei University, Seoul 03722 , Republic of Korea.
β-Hairpin peptides present great potential as antagonists against β-sheet-rich protein surfaces, of which wide and flat geometries are typically "undruggable" with small molecules. Herein, we introduce a peptide-dendrimer conjugate (PDC) approach that stabilizes the β-hairpin structure of the peptide via intermolecular forces and the excluded volume effect as well as exploits the multivalent binding effect. Because of the synergistic advantages, the PDCs based on a β-hairpin peptide isolated from an engineered programmed death-1 (PD-1) protein showed significantly higher affinity (avidity) to their binding counterpart, programmed death-ligand 1 (PD-L1), as compared to free peptides (by up to 5 orders of magnitude).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!