RVG Peptide-Functionalized Favipiravir Nanoparticle Delivery System Facilitates Antiviral Therapy of Neurotropic Virus Infection in a Mouse Model

Abstract

Neurotropic viruses severely damage the central nervous system (CNS) and human health. Common neurotropic viruses include rabies virus (RABV), Zika virus, and poliovirus. When treating neurotropic virus infection, obstruction of the blood–brain barrier (BBB) reduces the efficiency of drug delivery to the CNS. An efficient intracerebral delivery system can significantly increase intracerebral delivery efficiency and facilitate antiviral therapy. In this study, a rabies virus glycopeptide (RVG) functionalized mesoporous silica nanoparticle (MSN) packaging favipiravir (T-705) was developed to generate T-705@MSN-RVG. It was further evaluated for drug delivery and antiviral treatment in a VSV-infected mouse model. The RVG, a polypeptide consisting of 29 amino acids, was conjugated on the nanoparticle to enhance CNS delivery. The T-705@MSN-RVG caused a significant decrease in virus titers and virus proliferation without inducing substantial cell damage in vitro. By releasing T-705, the nanoparticle promoted viral inhibition in the brain during infection. At 21 days post-infection (dpi), a significantly enhanced survival ratio (77%) was observed in the group inoculated with nanoparticle compared with the non-treated group (23%). The viral RNA levels were also decreased in the therapy group at 4 and 6 dpi compared with that of the control group. The T-705@MSN-RVG could be considered a promising system for CNS delivery for treating neurotropic virus infection.

Pharmacogenomic Studies of Antiviral Drug Favipiravir

“…The rising interest in FAV is ascribed to its efficient suppression of dangerous and even lethal infections caused by numerous viruses, such as hemorrhagic fevers, COVID-19, SARS, MERS, rabies, etc. [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], and by its possible efficacy against viruses, which can be transferred to humans from animals and have a high epidemic potential [ 1 , 4 , 5 , 6 , 17 , 18 ]. Several drug preparations of FAV have been already developed and registered for clinical use (T-705, Avigan, Favilavir, Avifavir, Areplivir, Coronavir) [ 5 , 20 , 21 , 22 ] and many derivatives and analogs are under development (reviewed in [ 46 ]).…”

“…This synthetic analog of natural nucleobases shows efficacy against various RNA-containing viruses: orthomyxoviruses (human influenza type A, B and C viruses) [ 2 , 3 , 4 , 5 , 6 ], flaviviruses (Zika, denge and West-Nile fever viruses) [ 7 , 8 , 9 ], arboviruses (Rift Valley, Crimean-Congo fever viruses) [ 10 , 11 ], arenaviruses [ 12 ], paramyxo-, alpha-, bunya-, and noroviruses [ 13 , 14 ]. FAV was found relatively efficient against such dangerous pathogens as Ebola fever [ 15 ] and rabies viruses [ 16 ].…”

Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development

“…This would give us an overall picture that can be connected to understanding the pathology in question better. All this will bring us closer to finding future treatments for these pathologies; for example, using nanoparticles to deal with neurotrophic virus infections has been observed [280,281]. Considering all this, understanding what is happening with each cell to elucidate both a general and specific overview is highly relevant for the future when aiming to obtain specific targets for the treatment of the various neurological pathologies discussed in this article, from meningitis to neurodegenerative diseases such as AD.…”

Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti-MRSA Infection Activities for Zebrafish (Danio rerio)

“…The data were expressed as mean ± standard deviation (SD). Statistical analysis was performed using the GraphPad Prism 8 (version 8.0.2 (263)), Origin 2024 (version 10.1.0.178) and Image J (1.8.0_345) [58]. The statistical significance was analyzed by one-way ANOVA (and nonparametric or mixed) using GraphPad Prism software (version 8.0.2 (263)).…”