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Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP,...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675045/ https://www.ncbi.nlm.nih.gov/pubmed/38005839 http://dx.doi.org/10.3390/v15112161 |
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author | Gallardo-Toledo, Eduardo Neary, Megan Sharp, Joanne Herriott, Joanne Kijak, Edyta Bramwell, Chloe Curley, Paul Arshad, Usman Pertinez, Henry Rajoli, Rajith K. R. Valentijn, Anthony Cox, Helen Tatham, Lee Kipar, Anja Stewart, James P. Owen, Andrew |
author_facet | Gallardo-Toledo, Eduardo Neary, Megan Sharp, Joanne Herriott, Joanne Kijak, Edyta Bramwell, Chloe Curley, Paul Arshad, Usman Pertinez, Henry Rajoli, Rajith K. R. Valentijn, Anthony Cox, Helen Tatham, Lee Kipar, Anja Stewart, James P. Owen, Andrew |
author_sort | Gallardo-Toledo, Eduardo |
collection | PubMed |
description | Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed. |
format | Online Article Text |
id | pubmed-10675045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106750452023-10-27 Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters Gallardo-Toledo, Eduardo Neary, Megan Sharp, Joanne Herriott, Joanne Kijak, Edyta Bramwell, Chloe Curley, Paul Arshad, Usman Pertinez, Henry Rajoli, Rajith K. R. Valentijn, Anthony Cox, Helen Tatham, Lee Kipar, Anja Stewart, James P. Owen, Andrew Viruses Article Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed. MDPI 2023-10-27 /pmc/articles/PMC10675045/ /pubmed/38005839 http://dx.doi.org/10.3390/v15112161 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gallardo-Toledo, Eduardo Neary, Megan Sharp, Joanne Herriott, Joanne Kijak, Edyta Bramwell, Chloe Curley, Paul Arshad, Usman Pertinez, Henry Rajoli, Rajith K. R. Valentijn, Anthony Cox, Helen Tatham, Lee Kipar, Anja Stewart, James P. Owen, Andrew Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title | Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title_full | Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title_fullStr | Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title_full_unstemmed | Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title_short | Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters |
title_sort | chemoprophylactic assessment of combined intranasal sars-cov-2 polymerase and exonuclease inhibition in syrian golden hamsters |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675045/ https://www.ncbi.nlm.nih.gov/pubmed/38005839 http://dx.doi.org/10.3390/v15112161 |
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