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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/147122
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/147122
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:53:03Zoai: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:34982025-10-22 11:53:04.127CONICET 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
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-021-86679-0
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-021-86679-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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