Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

Abstract The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral ef...

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Autores principales:	C. Joaquín Cáceres, Stivalis Cardenas-Garcia, Silvia Carnaccini, Brittany Seibert, Daniela S. Rajao, Jun Wang, Daniel R. Perez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71d2e993765649be8e0f6b0bf79c99a9
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spelling	oai:doaj.org-article:71d2e993765649be8e0f6b0bf79c99a92021-12-02T15:38:12ZEfficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model10.1038/s41598-021-89013-w2045-2322https://doaj.org/article/71d2e993765649be8e0f6b0bf79c99a92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89013-whttps://doaj.org/toc/2045-2322Abstract The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 105 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 103 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.C. Joaquín CáceresStivalis Cardenas-GarciaSilvia CarnacciniBrittany SeibertDaniela S. RajaoJun WangDaniel R. PerezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. Joaquín Cáceres Stivalis Cardenas-Garcia Silvia Carnaccini Brittany Seibert Daniela S. Rajao Jun Wang Daniel R. Perez Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
description	Abstract The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 105 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 103 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.
format	article
author	C. Joaquín Cáceres Stivalis Cardenas-Garcia Silvia Carnaccini Brittany Seibert Daniela S. Rajao Jun Wang Daniel R. Perez
author_facet	C. Joaquín Cáceres Stivalis Cardenas-Garcia Silvia Carnaccini Brittany Seibert Daniela S. Rajao Jun Wang Daniel R. Perez
author_sort	C. Joaquín Cáceres
title	Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
title_short	Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
title_full	Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
title_fullStr	Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
title_full_unstemmed	Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
title_sort	efficacy of gc-376 against sars-cov-2 virus infection in the k18 hace2 transgenic mouse model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71d2e993765649be8e0f6b0bf79c99a9
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Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

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