Dengue virus (DENV) is the most prevalent mosquito-borne flavivirus that infects humans. At present, there are no specific antiviral drugs to treat DENV infection and vaccine development has met with challenges. DENV encodes two glycosaminoglycan (GAG) binding proteins; Envelope (E) and non-structural protein 1 (NS1). While previous work has validated the use of GAG analogues as inhibitors of E mediated virus-cell attachment, their potential for antiviral intervention in NS1 protein toxicity has not yet been explored. Here, we investigate the potential of the heparan sulfate mimetic PG545 as a dual purpose compound to target both DENV virion infectivity and NS1 function. In comparison to a non-sulfated analogue, we show that PG545 potently inhibits DENV infectivity with no cytotoxic effect. Against NS1, PG545 completely blocks the induction of cellular activation and abolishes NS1-mediated disruption of endothelial monolayer integrity. Furthermore, PG545 treatment moderately improves survival from lethal DENV challenge in a murine model. At peak disease, PG545-treated mice have lower viremia, circulating NS1 and serum TNF-α. Consistent with anti-NS1 activity, PG545 treatment also reduces systemic vascular leakage caused by DENV infection in vivo. Taken together, these findings demonstrate that the dual targeting of DENV virions and NS1 using GAG analogues offers a new avenue for DENV drug development.
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http://dx.doi.org/10.1016/j.antiviral.2019.05.004 | DOI Listing |
Vaccine X
January 2025
ALPS Global Holding Berhad, The ICON, East Wing Tower, No. 1, Jalan 1/68F, Off Jalan Tun Razak, Kuala Lumpur 50400, Malaysia.
Dengue fever is caused by the mosquito-borne dengue virus (DENV), which is endemic in more than 100 countries. Annually, there are approximately 390 million dengue cases, with a small subset manifesting into severe illnesses, such as dengue haemorrhagic fever or dengue shock syndrome. Current treatment options for dengue infections remain supportive management due to the lack of an effective vaccine and clinically approved antiviral.
View Article and Find Full Text PDFJ Membr Biol
January 2025
School of Chemistry, Sambalpur University, Jyoti Vihar, Burla, Odisha, 768 109, India.
Membrane fusion is the first step in the infection process of the enveloped viruses. Enveloped viruses fuse either at the cell surface or enter the cell through endocytosis and transfer their internal genetic materials by fusing with the endosomal membrane at acidic pH. In this work, we have evaluated the effect of the Dengue virus fusion peptide (DENV FP) on the polyethylene glycol (PEG)-mediated lipid mixing of vesicles (hemifusion formation) at pH 5 and pH 7.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Program of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Currently, no approved antiviral drugs target dengue virus (DENV) infection, leaving treatment reliant on supportive care. DENV vaccine efficacy varies depending on the vaccine type, the circulating serotype, and vaccine coverage. We investigated defective interfering particles (DIPs) and lipid nanoparticles (LNPs) to deliver DI290, an anti-DENV DI RNA.
View Article and Find Full Text PDFACS Appl Bio Mater
January 2025
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
In recent years, the increasing prevalence of viral infections such as dengue (DENV) and chikungunya (CHIKV) has emphasized the vital need for new diagnostic techniques that are not only quick and inexpensive but also suitable for point-of-care and home usage. Existing diagnostic procedures, while useful, sometimes have limits in terms of speed, mobility, and price, particularly in resource-constrained environments and during epidemics. To address these issues, this study proposes a novel technique that combines 3D printing technology with electrochemical biosensors to provide a highly sensitive, user-friendly, and customizable diagnostic platform.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Internal Medicine, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran.
Dengue virus (DENV) poses a considerable threat to public health on a global scale, since about two-thirds of the world's population is currently at risk of contracting this arbovirus. Being transmitted by mosquitoes, this virus is associated with a range of illnesses and a small percentage of infected individuals might suffer from severe vascular leakage. This leakage leads to hypovolemic shock syndrome, generally known as dengue shock syndrome, organ failure, and bleeding complications.
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