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Common neurotropic viruses include rabies virus (RABV), Zika virus, and poliovirus. When treating neurotropic virus infection, obstruction of the blood\u2013brain 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.<\/jats:p>","DOI":"10.3390\/ijms24065851","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["RVG Peptide-Functionalized Favipiravir Nanoparticle Delivery System Facilitates Antiviral Therapy of Neurotropic Virus Infection in a Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-8330","authenticated-orcid":false,"given":"Meishen","family":"Ren","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China"},{"name":"Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery (HKAP), Hong Kong SAR, China"},{"name":"Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-5509","authenticated-orcid":false,"given":"You","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Tu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-3685","authenticated-orcid":false,"given":"Dike","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maonan","family":"Pang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Human Health of Sichuan Province, Animal Quarantine Laboratory, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/13550280591002450","article-title":"The ecology of emerging neurotropic viruses","volume":"11","author":"Olival","year":"2005","journal-title":"J. Neurovirol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Masmejan, S., Musso, D., Vouga, M., Pomar, L., Dashraath, P., Stojanov, M., Panchaud, A., and Baud, D. (2020). Zika Virus. Pathogens, 9.","DOI":"10.3390\/pathogens9110898"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/B978-0-12-387040-7.00003-2","article-title":"Evasive strategies in rabies virus infection","volume":"79","author":"Lafon","year":"2011","journal-title":"Adv. Virus Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"662578","DOI":"10.3389\/fncel.2021.662578","article-title":"Neurotropic Viruses, Astrocytes, and COVID-19","volume":"15","author":"Potokar","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virusres.2013.06.003","article-title":"Understanding and altering cell tropism of vesicular stomatitis virus","volume":"176","author":"Hastie","year":"2013","journal-title":"Virus Res."},{"key":"ref_6","first-page":"1704","article-title":"Herpes Simplex Virus Infections of the Central Nervous System","volume":"21","author":"Whitley","year":"2015","journal-title":"Continuum"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"767104","DOI":"10.3389\/fmicb.2021.767104","article-title":"Functionalized Nanoparticles in Prevention and Targeted Therapy of Viral Diseases With Neurotropism Properties, Special Insight on COVID-19","volume":"12","author":"Ren","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1039\/C6CS00076B","article-title":"Blood-brain barrier shuttle peptides: An emerging paradigm for brain delivery","volume":"45","author":"Giralt","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1695","DOI":"10.1002\/wnan.1695","article-title":"Brain penetrating peptides and peptide-drug conjugates to overcome the blood-brain barrier and target CNS diseases","volume":"13","author":"Zhou","year":"2021","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.msec.2017.12.029","article-title":"Targeted transport of nanocarriers into brain for theranosis with rabies virus glycoprotein-derived peptide","volume":"87","author":"Fu","year":"2018","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2183\/pjab.93.027","article-title":"Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase","volume":"93","author":"Furuta","year":"2017","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1016\/j.vaccine.2018.04.003","article-title":"The effect of combined drugs therapy on the course of clinical rabies infection in a murine model","volume":"37","author":"Smreczak","year":"2019","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mendenhall, M., Russell, A., Smee, D.F., Hall, J.O., Skirpstunas, R., Furuta, Y., and Gowen, B.B. (2011). Effective oral favipiravir (T-705) therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001342"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1093\/infdis\/jiv586","article-title":"Efficacy of Favipiravir (T-705) in Rabies Postexposure Prophylaxis","volume":"213","author":"Yamada","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zmurko, J., Marques, R.E., Schols, D., Verbeken, E., Kaptein, S.J., and Neyts, J. (2016). The Viral Polymerase Inhibitor 7-Deaza-2\u2032-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004695"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2020.05.034","article-title":"Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase","volume":"182","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1016\/j.vaccine.2017.10.109","article-title":"Re-evaluating the effect of Favipiravir treatment on rabies virus infection","volume":"37","author":"Banyard","year":"2019","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128557","DOI":"10.1016\/j.cej.2021.128557","article-title":"Aptamer and RVG functionalized gold nanorods for targeted photothermal therapy of neurotropic virus infection in the mouse brain","volume":"411","author":"Ren","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nature05901","article-title":"Transvascular delivery of small interfering RNA to the central nervous system","volume":"448","author":"Kumar","year":"2007","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1016\/j.biomaterials.2009.02.051","article-title":"Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles","volume":"30","author":"Liu","year":"2009","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1053\/tvjl.1998.0303","article-title":"Vesicular stomatitis","volume":"157","author":"Letchworth","year":"1999","journal-title":"Vet. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15414","DOI":"10.1073\/pnas.1110854108","article-title":"Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors","volume":"108","author":"Beier","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.virol.2018.06.018","article-title":"Chikungunya-vesicular stomatitis chimeric virus targets and eliminates brain tumors","volume":"522","author":"Zhang","year":"2018","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.chom.2020.07.018","article-title":"Replication-Competent Vesicular Stomatitis Virus Vaccine Vector Protects against SARS-CoV-2-Mediated Pathogenesis in Mice","volume":"28","author":"Case","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1056\/NEJMoa1414216","article-title":"A Recombinant Vesicular Stomatitis Virus Ebola Vaccine","volume":"376","author":"Regules","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/path.4461","article-title":"The olfactory nerve: A shortcut for influenza and other viral diseases into the central nervous system","volume":"235","author":"Verdijk","year":"2015","journal-title":"J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1073\/pnas.1811345115","article-title":"The mechanism of resistance to favipiravir in influenza","volume":"115","author":"Goldhill","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00487","DOI":"10.1128\/JVI.00487-17","article-title":"Understanding the Mechanism of the Broad-Spectrum Antiviral Activity of Favipiravir (T-705): Key Role of the F1 Motif of the Viral Polymerase","volume":"91","author":"Abdelnabi","year":"2017","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lowe, D.M., Brown, L.K., Chowdhury, K., Davey, S., Yee, P., Ikeji, F., Ndoutoumou, A., Shah, D., Lennon, A., and Rai, A. (2022). Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 \u00d7 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19. PLoS Med., 19.","DOI":"10.1101\/2022.02.11.22270775"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104641","DOI":"10.1016\/j.antiviral.2019.104641","article-title":"Reevaluation of the efficacy of favipiravir against rabies virus using in vivo imaging analysis","volume":"172","author":"Yamada","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1605563","DOI":"10.1002\/adma.201605563","article-title":"Rabies Virus-Inspired Silica-Coated Gold Nanorods as a Photothermal Therapeutic Platform for Treating Brain Tumors","volume":"29","author":"Lee","year":"2017","journal-title":"Adv. Mater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1124\/pr.54.4.561","article-title":"Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway","volume":"54","author":"Qian","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.antiviral.2009.02.198","article-title":"T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections","volume":"82","author":"Furuta","year":"2009","journal-title":"Antiviral Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s13059-020-02150-9","article-title":"A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation","volume":"21","author":"Sui","year":"2020","journal-title":"Genome Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3389\/fimmu.2019.00429","article-title":"Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers","volume":"10","author":"Luo","year":"2019","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:58:51Z","timestamp":1760122731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,19]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065851"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065851","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,19]]}}}