{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:41:26Z","timestamp":1759506086699,"version":"build-2065373602"},"reference-count":16,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sao Paulo Research Foundation","award":["2022\/07115-7"],"award-info":[{"award-number":["2022\/07115-7"]}]},{"name":"Sao Paulo Research Foundation","award":["302503 2021-8"],"award-info":[{"award-number":["302503 2021-8"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["2022\/07115-7"],"award-info":[{"award-number":["2022\/07115-7"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["302503 2021-8"],"award-info":[{"award-number":["302503 2021-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Inst. Med. trop. S. Paulo"],"abstract":"<jats:p>ABSTRACT Despite its 100% lethality and approximately 59,000 human deaths every year, rabies still lacks an effective treatment. Numerous trials have aimed to impair the life cycle of Lyssavirus rabies (RABV), the primary worldwide lyssavirus causing rabies, but with limited success. Treatments targeting host factors and attempting to mitigate the damage caused by RABV have also been unsatisfactory. This article describes the effects of intracerebral transfection of anti-RABV recombinant monoclonal nanobodies as antivirals against rabies in vivo, in a post-exposure protocol. Mice were intranasally inoculated with the RABV CVS strain and, 72 h later, were injected via the intracerebral route with two different anti-RABV llama-derived VHH nanobodies complexed with a transfection agent. One of the VHHs was able to reduce the viral load in mice, but no significant effect on survival was detected. Though not completely effective, nanobody therapy could be attempted in association with other antivirals to improve therapies against rabies.<\/jats:p>","DOI":"10.1590\/s1678-9946202567063","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:05:49Z","timestamp":1759503949000},"source":"Crossref","is-referenced-by-count":0,"title":["Nanobodies as antivirals against rabies in experimentally infected mice"],"prefix":"10.1590","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8576-842X","authenticated-orcid":false,"given":"Washington Carlos","family":"Agostinho","sequence":"first","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-5592","authenticated-orcid":false,"given":"Viviana","family":"Parre\u00f1o","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Tecnolog\u00eda Agropecuaria,  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0644-7263","authenticated-orcid":false,"given":"Celina Guadalupe","family":"Vega","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Tecnolog\u00eda Agropecuaria,  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9464-1401","authenticated-orcid":false,"given":"Matias","family":"Aduriz","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Tecnolog\u00eda Agropecuaria,  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1987-0037","authenticated-orcid":false,"given":"Carolina Moura de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-0009","authenticated-orcid":false,"given":"Sheila Olivera de Sousa","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1304-1608","authenticated-orcid":false,"given":"Joana","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-7015","authenticated-orcid":false,"given":"Sueli Akemi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-7839","authenticated-orcid":false,"given":"Paulo Eduardo","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo,  Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"key":"ref1","series-title":"Rabies"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S1474-4422(13)70038-3","article-title":"Human rabies: neuropathogenesis, diagnosis, and management","volume":"12","author":"Hemachudha T","year":"2013","journal-title":"Lancet Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1017\/cjn.2015.331","article-title":"Critical appraisal of the Milwaukee protocol for rabies: this failed approach should be abandoned","volume":"43","author":"Zeiler F A","year":"2016","journal-title":"Can J Neurol Sci"},{"key":"ref4","article-title":"A combination of two human monoclonal antibodies cures symptomatic rabies","volume":"12","author":"Melo GD","year":"2020","journal-title":"EMBO Mol Med"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0109367","article-title":"Protective effect of different anti-rabies virus VHH constructs against rabies disease in mice","volume":"9","author":"Terryn S","year":"2014","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ebiom.2016.04.028","article-title":"Nanobodies as versatile tools to understand, diagnose, visualize and treat cancer","volume":"8","author":"Van Audenhove I","year":"2016","journal-title":"EBioMedicine"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/imr.13381","article-title":"Single domain antibody: development and application in biotechnology and biopharma","volume":"328","author":"Yu T","year":"2024","journal-title":"Immunol Rev"},{"key":"ref8","series-title":"Laboratory techniques in rabies","first-page":"88","volume-title":"The fluorescent antibody test","author":"Dean DJ","year":"1996","edition":"4"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jviromet.2011.07.002","article-title":"A universal real-time assay for the detection of Lyssaviruses","volume":"177","author":"Hayman DT","year":"2011","journal-title":"J Virol Methods"},{"key":"ref10","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens11121556","article-title":"Evolution of rabies virus isolates: virulence signatures and effects of modulation by neutralizing antibodies","volume":"11","author":"Conselheiro JA","year":"2022","journal-title":"Pathogens"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.bjm.2016.11.007","article-title":"Short interfering RNAs targeting a vampire-bat related rabies virus phosphoprotein mRNA","volume":"48","author":"Ono EA","year":"2017","journal-title":"Braz J 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