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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Autor*in:	Eduardo Gallardo-Toledo [verfasserIn] Megan Neary [verfasserIn] Joanne Sharp [verfasserIn] Joanne Herriott [verfasserIn] Edyta Kijak [verfasserIn] Chloe Bramwell [verfasserIn] Paul Curley [verfasserIn] Usman Arshad [verfasserIn] Henry Pertinez [verfasserIn] Rajith K. R. Rajoli [verfasserIn] Anthony Valentijn [verfasserIn] Helen Cox [verfasserIn] Lee Tatham [verfasserIn] Anja Kipar [verfasserIn] James P. Stewart [verfasserIn] Andrew Owen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis

Übergeordnetes Werk:	In: Viruses - MDPI AG, 2009, 15(2023), 11, p 2161
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:11, p 2161

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/v15112161

Katalog-ID:	DOAJ10117960X

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allfields	10.3390/v15112161 doi (DE-627)DOAJ10117960X (DE-599)DOAJ2abae7604c2149b0bf1d2616a2ba6281 DE-627 ger DE-627 rakwb eng QR1-502 Eduardo Gallardo-Toledo verfasserin aut Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology Megan Neary verfasserin aut Joanne Sharp verfasserin aut Joanne Herriott verfasserin aut Edyta Kijak verfasserin aut Chloe Bramwell verfasserin aut Paul Curley verfasserin aut Usman Arshad verfasserin aut Henry Pertinez verfasserin aut Rajith K. R. Rajoli verfasserin aut Anthony Valentijn verfasserin aut Helen Cox verfasserin aut Lee Tatham verfasserin aut Anja Kipar verfasserin aut James P. Stewart verfasserin aut Andrew Owen verfasserin aut In Viruses MDPI AG, 2009 15(2023), 11, p 2161 (DE-627)609775871 (DE-600)2516098-9 19994915 nnns volume:15 year:2023 number:11, p 2161 https://doi.org/10.3390/v15112161 kostenfrei https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 kostenfrei https://www.mdpi.com/1999-4915/15/11/2161 kostenfrei https://doaj.org/toc/1999-4915 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 11, p 2161
spelling	10.3390/v15112161 doi (DE-627)DOAJ10117960X (DE-599)DOAJ2abae7604c2149b0bf1d2616a2ba6281 DE-627 ger DE-627 rakwb eng QR1-502 Eduardo Gallardo-Toledo verfasserin aut Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology Megan Neary verfasserin aut Joanne Sharp verfasserin aut Joanne Herriott verfasserin aut Edyta Kijak verfasserin aut Chloe Bramwell verfasserin aut Paul Curley verfasserin aut Usman Arshad verfasserin aut Henry Pertinez verfasserin aut Rajith K. R. Rajoli verfasserin aut Anthony Valentijn verfasserin aut Helen Cox verfasserin aut Lee Tatham verfasserin aut Anja Kipar verfasserin aut James P. Stewart verfasserin aut Andrew Owen verfasserin aut In Viruses MDPI AG, 2009 15(2023), 11, p 2161 (DE-627)609775871 (DE-600)2516098-9 19994915 nnns volume:15 year:2023 number:11, p 2161 https://doi.org/10.3390/v15112161 kostenfrei https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 kostenfrei https://www.mdpi.com/1999-4915/15/11/2161 kostenfrei https://doaj.org/toc/1999-4915 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 11, p 2161
allfields_unstemmed	10.3390/v15112161 doi (DE-627)DOAJ10117960X (DE-599)DOAJ2abae7604c2149b0bf1d2616a2ba6281 DE-627 ger DE-627 rakwb eng QR1-502 Eduardo Gallardo-Toledo verfasserin aut Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology Megan Neary verfasserin aut Joanne Sharp verfasserin aut Joanne Herriott verfasserin aut Edyta Kijak verfasserin aut Chloe Bramwell verfasserin aut Paul Curley verfasserin aut Usman Arshad verfasserin aut Henry Pertinez verfasserin aut Rajith K. R. Rajoli verfasserin aut Anthony Valentijn verfasserin aut Helen Cox verfasserin aut Lee Tatham verfasserin aut Anja Kipar verfasserin aut James P. Stewart verfasserin aut Andrew Owen verfasserin aut In Viruses MDPI AG, 2009 15(2023), 11, p 2161 (DE-627)609775871 (DE-600)2516098-9 19994915 nnns volume:15 year:2023 number:11, p 2161 https://doi.org/10.3390/v15112161 kostenfrei https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 kostenfrei https://www.mdpi.com/1999-4915/15/11/2161 kostenfrei https://doaj.org/toc/1999-4915 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 11, p 2161
allfieldsGer	10.3390/v15112161 doi (DE-627)DOAJ10117960X (DE-599)DOAJ2abae7604c2149b0bf1d2616a2ba6281 DE-627 ger DE-627 rakwb eng QR1-502 Eduardo Gallardo-Toledo verfasserin aut Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology Megan Neary verfasserin aut Joanne Sharp verfasserin aut Joanne Herriott verfasserin aut Edyta Kijak verfasserin aut Chloe Bramwell verfasserin aut Paul Curley verfasserin aut Usman Arshad verfasserin aut Henry Pertinez verfasserin aut Rajith K. R. Rajoli verfasserin aut Anthony Valentijn verfasserin aut Helen Cox verfasserin aut Lee Tatham verfasserin aut Anja Kipar verfasserin aut James P. Stewart verfasserin aut Andrew Owen verfasserin aut In Viruses MDPI AG, 2009 15(2023), 11, p 2161 (DE-627)609775871 (DE-600)2516098-9 19994915 nnns volume:15 year:2023 number:11, p 2161 https://doi.org/10.3390/v15112161 kostenfrei https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 kostenfrei https://www.mdpi.com/1999-4915/15/11/2161 kostenfrei https://doaj.org/toc/1999-4915 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 11, p 2161
allfieldsSound	10.3390/v15112161 doi (DE-627)DOAJ10117960X (DE-599)DOAJ2abae7604c2149b0bf1d2616a2ba6281 DE-627 ger DE-627 rakwb eng QR1-502 Eduardo Gallardo-Toledo verfasserin aut Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology Megan Neary verfasserin aut Joanne Sharp verfasserin aut Joanne Herriott verfasserin aut Edyta Kijak verfasserin aut Chloe Bramwell verfasserin aut Paul Curley verfasserin aut Usman Arshad verfasserin aut Henry Pertinez verfasserin aut Rajith K. R. Rajoli verfasserin aut Anthony Valentijn verfasserin aut Helen Cox verfasserin aut Lee Tatham verfasserin aut Anja Kipar verfasserin aut James P. Stewart verfasserin aut Andrew Owen verfasserin aut In Viruses MDPI AG, 2009 15(2023), 11, p 2161 (DE-627)609775871 (DE-600)2516098-9 19994915 nnns volume:15 year:2023 number:11, p 2161 https://doi.org/10.3390/v15112161 kostenfrei https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 kostenfrei https://www.mdpi.com/1999-4915/15/11/2161 kostenfrei https://doaj.org/toc/1999-4915 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 11, p 2161
language	English
source	In Viruses 15(2023), 11, p 2161 volume:15 year:2023 number:11, p 2161
sourceStr	In Viruses 15(2023), 11, p 2161 volume:15 year:2023 number:11, p 2161
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis Microbiology
isfreeaccess_bool	true
container_title	Viruses
authorswithroles_txt_mv	Eduardo Gallardo-Toledo @@aut@@ Megan Neary @@aut@@ Joanne Sharp @@aut@@ Joanne Herriott @@aut@@ Edyta Kijak @@aut@@ Chloe Bramwell @@aut@@ Paul Curley @@aut@@ Usman Arshad @@aut@@ Henry Pertinez @@aut@@ Rajith K. R. Rajoli @@aut@@ Anthony Valentijn @@aut@@ Helen Cox @@aut@@ Lee Tatham @@aut@@ Anja Kipar @@aut@@ James P. Stewart @@aut@@ Andrew Owen @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	609775871
id	DOAJ10117960X
language_de	englisch
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callnumber-first	Q - Science
author	Eduardo Gallardo-Toledo
spellingShingle	Eduardo Gallardo-Toledo misc QR1-502 misc SARS-CoV-2 misc pibrentasvir misc favipiravir misc remdesivir misc chemoprophylaxis misc Microbiology Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
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topic_title	QR1-502 Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters SARS-CoV-2 pibrentasvir favipiravir remdesivir chemoprophylaxis
topic	misc QR1-502 misc SARS-CoV-2 misc pibrentasvir misc favipiravir misc remdesivir misc chemoprophylaxis misc Microbiology
topic_unstemmed	misc QR1-502 misc SARS-CoV-2 misc pibrentasvir misc favipiravir misc remdesivir misc chemoprophylaxis misc Microbiology
topic_browse	misc QR1-502 misc SARS-CoV-2 misc pibrentasvir misc favipiravir misc remdesivir misc chemoprophylaxis misc Microbiology
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title	Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
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title_full	Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
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author_browse	Eduardo Gallardo-Toledo Megan Neary Joanne Sharp Joanne Herriott Edyta Kijak Chloe Bramwell Paul Curley Usman Arshad Henry Pertinez Rajith K. R. Rajoli Anthony Valentijn Helen Cox Lee Tatham Anja Kipar James P. Stewart Andrew Owen
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title_sort	chemoprophylactic assessment of combined intranasal sars-cov-2 polymerase and exonuclease inhibition in syrian golden hamsters
callnumber	QR1-502
title_auth	Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
abstract	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.
abstractGer	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.
abstract_unstemmed	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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title_short	Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
url	https://doi.org/10.3390/v15112161 https://doaj.org/article/2abae7604c2149b0bf1d2616a2ba6281 https://www.mdpi.com/1999-4915/15/11/2161 https://doaj.org/toc/1999-4915
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up_date	2024-07-03T19:06:14.451Z
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Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters

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