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Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treat...
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| Published in: | Scientific reports 2021-03, Vol.11 (1), p.7132-7132, Article 7132 |
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| creator | Arévalo, A. P. Pagotto, R. Pórfido, J. L. Daghero, H. Segovia, M. Yamasaki, K. Varela, B. Hill, M. Verdes, J. M. Duhalde Vega, M. Bollati-Fogolín, M. Crispo, M. |
| description | The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p |
| doi_str_mv | 10.1038/s41598-021-86679-0 |
| format | article |
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P. ; Pagotto, R. ; Pórfido, J. L. ; Daghero, H. ; Segovia, M. ; Yamasaki, K. ; Varela, B. ; Hill, M. ; Verdes, J. M. ; Duhalde Vega, M. ; Bollati-Fogolín, M. ; Crispo, M.</creator><creatorcontrib>Arévalo, A. P. ; Pagotto, R. ; Pórfido, J. L. ; Daghero, H. ; Segovia, M. ; Yamasaki, K. ; Varela, B. ; Hill, M. ; Verdes, J. M. ; Duhalde Vega, M. ; Bollati-Fogolín, M. ; Crispo, M.</creatorcontrib><description>The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-86679-0</identifier><identifier>PMID: 33785846</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/1807 ; 692/699 ; Alanine ; Alanine transaminase ; Animals ; Antiviral Agents - administration & dosage ; Antiviral Agents - pharmacology ; Aspartate aminotransferase ; Body Weight - drug effects ; Coronaviridae ; Coronavirus Infections - drug therapy ; Coronavirus Infections - pathology ; Coronavirus Infections - virology ; Coronaviruses ; COVID-19 ; Disease Models, Animal ; Female ; Hepatitis ; Humanities and Social Sciences ; Infections ; Inflammation ; Ivermectin ; Ivermectin - administration & dosage ; Ivermectin - pharmacology ; Kidney - drug effects ; Kidney - metabolism ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver - virology ; Mice ; Mice, Inbred BALB C ; Monocytes - drug effects ; multidisciplinary ; Murine hepatitis virus - pathogenicity ; Neutrophils - drug effects ; Proteins - metabolism ; Science ; Science (multidisciplinary) ; Severe acute respiratory syndrome coronavirus 2 ; Transaminase ; Transaminases - metabolism ; Tumor Necrosis Factor-alpha - blood ; Viral infections ; Viral Load - drug effects</subject><ispartof>Scientific reports, 2021-03, Vol.11 (1), p.7132-7132, Article 7132</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-6b55da1a71e5b3315d3a0e3694ff4c017235547465880dc0d40c2e1cf8e78c43</citedby><cites>FETCH-LOGICAL-c540t-6b55da1a71e5b3315d3a0e3694ff4c017235547465880dc0d40c2e1cf8e78c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2506941174/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2506941174?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33785846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arévalo, A. P.</creatorcontrib><creatorcontrib>Pagotto, R.</creatorcontrib><creatorcontrib>Pórfido, J. L.</creatorcontrib><creatorcontrib>Daghero, H.</creatorcontrib><creatorcontrib>Segovia, M.</creatorcontrib><creatorcontrib>Yamasaki, K.</creatorcontrib><creatorcontrib>Varela, B.</creatorcontrib><creatorcontrib>Hill, M.</creatorcontrib><creatorcontrib>Verdes, J. M.</creatorcontrib><creatorcontrib>Duhalde Vega, M.</creatorcontrib><creatorcontrib>Bollati-Fogolín, M.</creatorcontrib><creatorcontrib>Crispo, M.</creatorcontrib><title>Ivermectin reduces in vivo coronavirus infection in a mouse experimental model</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.</description><subject>692/1807</subject><subject>692/699</subject><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Animals</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - pharmacology</subject><subject>Aspartate aminotransferase</subject><subject>Body Weight - drug effects</subject><subject>Coronaviridae</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - pathology</subject><subject>Coronavirus Infections - virology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Hepatitis</subject><subject>Humanities and Social Sciences</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Ivermectin</subject><subject>Ivermectin - administration & dosage</subject><subject>Ivermectin - pharmacology</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver - virology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Monocytes - drug effects</subject><subject>multidisciplinary</subject><subject>Murine hepatitis virus - pathogenicity</subject><subject>Neutrophils - drug effects</subject><subject>Proteins - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Transaminase</subject><subject>Transaminases - metabolism</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><subject>Viral infections</subject><subject>Viral Load - drug effects</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kc1u1TAQhS1ERau2L8ACRWLDJjD-i50NEqpauFIFm-4tx55ccpXEFzuJ4O1xmlJaFnhja-bM55k5hLym8J4C1x-SoLLWJTBa6qpSdQkvyBkDIUvGGXv55H1KLlM6QD6S1YLWr8gp50pLLaoz8nW3YBzQTd1YRPSzw1Tk59ItoXAhhtEuXZzXWLuKwrhmbTGEOWGBP48YuwHHyfY55LG_ICet7RNePtzn5O7m-u7qS3n77fPu6tNt6aSAqawaKb2lVlGUDedUem4BeVWLthUOqGJcSqFEJbUG78ALcAypazUq7QQ_J7sN64M9mGPuwcZfJtjO3AdC3Bsbp871aGglrPOyaaRoRCuaBl3mtLXI2wOLPrM-bqzj3AzoXZ4m2v4Z9Hlm7L6bfViMBgog6gx49wCI4ceMaTJDlxz2vR0xr8kwCapSFGqdpW__kR7CHMe8qVWVx6dUrdOxTeViSCli-9gMBbOabzbzTTbf3JtvIBe9eTrGY8kfq7OAb4KUU-Me49-__4P9Db52uwg</recordid><startdate>20210330</startdate><enddate>20210330</enddate><creator>Arévalo, A. 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P. ; Pagotto, R. ; Pórfido, J. L. ; Daghero, H. ; Segovia, M. ; Yamasaki, K. ; Varela, B. ; Hill, M. ; Verdes, J. 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P.</au><au>Pagotto, R.</au><au>Pórfido, J. L.</au><au>Daghero, H.</au><au>Segovia, M.</au><au>Yamasaki, K.</au><au>Varela, B.</au><au>Hill, M.</au><au>Verdes, J. M.</au><au>Duhalde Vega, M.</au><au>Bollati-Fogolín, M.</au><au>Crispo, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ivermectin reduces in vivo coronavirus infection in a mouse experimental model</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2021-03-30</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>7132</spage><epage>7132</epage><pages>7132-7132</pages><artnum>7132</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33785846</pmid><doi>10.1038/s41598-021-86679-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 692/1807 692/699 Alanine Alanine transaminase Animals Antiviral Agents - administration & dosage Antiviral Agents - pharmacology Aspartate aminotransferase Body Weight - drug effects Coronaviridae Coronavirus Infections - drug therapy Coronavirus Infections - pathology Coronavirus Infections - virology Coronaviruses COVID-19 Disease Models, Animal Female Hepatitis Humanities and Social Sciences Infections Inflammation Ivermectin Ivermectin - administration & dosage Ivermectin - pharmacology Kidney - drug effects Kidney - metabolism Liver - drug effects Liver - metabolism Liver - pathology Liver - virology Mice Mice, Inbred BALB C Monocytes - drug effects multidisciplinary Murine hepatitis virus - pathogenicity Neutrophils - drug effects Proteins - metabolism Science Science (multidisciplinary) Severe acute respiratory syndrome coronavirus 2 Transaminase Transaminases - metabolism Tumor Necrosis Factor-alpha - blood Viral infections Viral Load - drug effects |
| title | Ivermectin reduces in vivo coronavirus infection in a mouse experimental model |
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