Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
- Autores
- Arevalo, A. P.; Pagotto, R.; Pórfido, Jorge Luis; Daghero, H.; Segovia, Alcira Mercedes; Yamasaki, K.; Varela, B; Hill, Marcelo; Verdes, J. M.; Duhalde Vega, Maite; Bollati Fogollin, M.; Crispo, Martina
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.
Fil: Arevalo, A. P.. Instituto Pasteur de Montevideo; Uruguay
Fil: Pagotto, R.. Instituto Pasteur de Montevideo; Uruguay
Fil: Pórfido, Jorge Luis. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Daghero, H.. Instituto Pasteur de Montevideo; Uruguay
Fil: Segovia, Alcira Mercedes. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Yamasaki, K.. Universidad de la Republica. Facultad de Veterinaria.; Uruguay
Fil: Varela, B. Universidad de la Republica. Facultad de Veterinaria.; Uruguay
Fil: Hill, Marcelo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Verdes, J. M.. Universidad de la Republica. Facultad de Veterinaria.; Uruguay
Fil: Duhalde Vega, Maite. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Bollati Fogollin, M.. Instituto Pasteur de Montevideo; Uruguay
Fil: Crispo, Martina. Instituto Pasteur de Montevideo; Uruguay - Materia
-
ivermectin
Coronavirus
Sars-Cov-2
COVID-19 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/147122
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Ivermectin reduces in vivo coronavirus infection in a mouse experimental modelArevalo, A. P.Pagotto, R.Pórfido, Jorge LuisDaghero, H.Segovia, Alcira MercedesYamasaki, K.Varela, BHill, MarceloVerdes, J. M.Duhalde Vega, MaiteBollati Fogollin, M.Crispo, MartinaivermectinCoronavirusSars-Cov-2COVID-19https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.Fil: Arevalo, A. P.. Instituto Pasteur de Montevideo; UruguayFil: Pagotto, R.. Instituto Pasteur de Montevideo; UruguayFil: Pórfido, Jorge Luis. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Daghero, H.. Instituto Pasteur de Montevideo; UruguayFil: Segovia, Alcira Mercedes. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Yamasaki, K.. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Varela, B. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Hill, Marcelo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Verdes, J. M.. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Duhalde Vega, Maite. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Bollati Fogollin, M.. Instituto Pasteur de Montevideo; UruguayFil: Crispo, Martina. Instituto Pasteur de Montevideo; UruguayNature Research2021-03-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/147122Arevalo, A. P.; Pagotto, R.; Pórfido, Jorge Luis; Daghero, H.; Segovia, Alcira Mercedes; et al.; Ivermectin reduces in vivo coronavirus infection in a mouse experimental model; Nature Research; Scientific Reports; 11; 7132; 30-3-2021; 1-122045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-021-86679-0info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-021-86679-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:20:24Zoai:ri.conicet.gov.ar:11336/147122instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:20:25.216CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
title |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
spellingShingle |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model Arevalo, A. P. ivermectin Coronavirus Sars-Cov-2 COVID-19 |
title_short |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
title_full |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
title_fullStr |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
title_full_unstemmed |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
title_sort |
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
dc.creator.none.fl_str_mv |
Arevalo, A. P. Pagotto, R. Pórfido, Jorge Luis Daghero, H. Segovia, Alcira Mercedes Yamasaki, K. Varela, B Hill, Marcelo Verdes, J. M. Duhalde Vega, Maite Bollati Fogollin, M. Crispo, Martina |
author |
Arevalo, A. P. |
author_facet |
Arevalo, A. P. Pagotto, R. Pórfido, Jorge Luis Daghero, H. Segovia, Alcira Mercedes Yamasaki, K. Varela, B Hill, Marcelo Verdes, J. M. Duhalde Vega, Maite Bollati Fogollin, M. Crispo, Martina |
author_role |
author |
author2 |
Pagotto, R. Pórfido, Jorge Luis Daghero, H. Segovia, Alcira Mercedes Yamasaki, K. Varela, B Hill, Marcelo Verdes, J. M. Duhalde Vega, Maite Bollati Fogollin, M. Crispo, Martina |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
ivermectin Coronavirus Sars-Cov-2 COVID-19 |
topic |
ivermectin Coronavirus Sars-Cov-2 COVID-19 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases. Fil: Arevalo, A. P.. Instituto Pasteur de Montevideo; Uruguay Fil: Pagotto, R.. Instituto Pasteur de Montevideo; Uruguay Fil: Pórfido, Jorge Luis. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Daghero, H.. Instituto Pasteur de Montevideo; Uruguay Fil: Segovia, Alcira Mercedes. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Yamasaki, K.. Universidad de la Republica. Facultad de Veterinaria.; Uruguay Fil: Varela, B. Universidad de la Republica. Facultad de Veterinaria.; Uruguay Fil: Hill, Marcelo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Verdes, J. M.. Universidad de la Republica. Facultad de Veterinaria.; Uruguay Fil: Duhalde Vega, Maite. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Bollati Fogollin, M.. Instituto Pasteur de Montevideo; Uruguay Fil: Crispo, Martina. Instituto Pasteur de Montevideo; Uruguay |
description |
SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-03-30 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/147122 Arevalo, A. P.; Pagotto, R.; Pórfido, Jorge Luis; Daghero, H.; Segovia, Alcira Mercedes; et al.; Ivermectin reduces in vivo coronavirus infection in a mouse experimental model; Nature Research; Scientific Reports; 11; 7132; 30-3-2021; 1-12 2045-2322 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/147122 |
identifier_str_mv |
Arevalo, A. P.; Pagotto, R.; Pórfido, Jorge Luis; Daghero, H.; Segovia, Alcira Mercedes; et al.; Ivermectin reduces in vivo coronavirus infection in a mouse experimental model; Nature Research; Scientific Reports; 11; 7132; 30-3-2021; 1-12 2045-2322 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
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Nature Research |
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Nature Research |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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