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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,...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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