SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice

Simple item page
dc.contributor.authorPavan, María Florenciaen
dc.contributor.authorBok, Marinaen
dc.contributor.authorBetanzos San Juan, Rafaelen
dc.contributor.authorMalito, Juan Pabloen
dc.contributor.authorMarcoppido, Gisela Arianaen
dc.contributor.authorFranco, Diego Rafaelen
dc.contributor.authorMilitelo, Daniela Ayelenen
dc.contributor.authorSchammas, Juan Manuelen
dc.contributor.authorBari, Sara Elizabethen
dc.contributor.authorStone, Williamen
dc.contributor.authorLópez, Krisangelen
dc.contributor.authorPorier, Danielle LaBrieen
dc.contributor.authorMuller, John Anthonyen
dc.contributor.authorAuguste, Albert Jonathanen
dc.contributor.authorYuan, Lijuanen
dc.contributor.authorWigdorovitz, Andrésen
dc.contributor.authorParreño, Viviana Gladysen
dc.contributor.authorIbañez, Lorena Itaten
dc.date.accessioned2024-02-23T15:18:00Zen
dc.date.available2024-02-23T15:18:00Zen
dc.date.issued2024-01-25en
dc.date.updated2024-02-23T15:03:11Zen
dc.description.abstractSince the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPavan, M.F.; Bok, M.; Betanzos San Juan, R.; Malito, J.P.; Marcoppido, G.A.; Franco, D.R.; Militelo, D.A.; Schammas, J.M.; Bari, S.E.; Stone, W.; López, K.; Porier, D.L.; Muller, J.A.; Auguste, A.J.; Yuan, L.; Wigdorovitz, A.; Parreño, V.G.; Ibañez, L.I. SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice. Viruses 2024, 16, 185.en
dc.identifier.doihttps://doi.org/10.3390/v16020185en
dc.identifier.urihttps://hdl.handle.net/10919/118126en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Miceen
dc.title.serialVirusesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
viruses-16-00185.pdf
Size:
5.74 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download
License bundle
Now showing 1 - 1 of 1
Name:
license.txt
Size:
1.5 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)
Scholarly Works, Biomedical Sciences and Pathobiology
Scholarly Works, Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP)
Scholarly Works, Entomology
Scholarly Works, Fralin Life Sciences Institute