Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
2021
Arévalo, Ana Paula | Pagotto, Romina | Pórfido Barayoli, Jorge Luis | Daghero Villanueva, Hellen | Segovia, Mercedes | Yamasaki, Kanji | Varela Cruces, María Belén | Hill, Marcelo | Verdes García, José Manuel | Duhalde Vega, Maite | Bollati-Fogolín, Mariela | Crispo, Martina | Arévalo Ana Paula, Institut Pasteur de Montevideo (Uruguay). Transgenic and Experimental Animal Unit | Pagotto Romina, Institut Pasteur de Montevideo (Uruguay). Cell Biology Unit | Pórfido Barayoli Jorge Luis, Institut Pasteur de Montevideo (Uruguay). Transgenic and Experimental Animal Unit / Institut Pasteur de Montevideo (Uruguay). Worm Biology Laboratory / Universidad de la República (Uruguay). Faculty of Chemistry. Department of Biosciences | Daghero Villanueva Hellen, Institut Pasteur de Montevideo (Uruguay). Cell Biology Unit | Segovia Mercedes, Institut Pasteur de Montevideo (Uruguay). Laboratory of Immunoregulation and Inflammation / Universidad de la República (Uruguay). Faculty of Medicine. Immunobiology Department | Yamasaki Kanji, Universidad de la República (Uruguay). Veterinary Faculty. Department of Pathobiology. Pathology Unit | Varela Cruces María Belén, Universidad de la República (Uruguay). Veterinary Faculty. Department of Pathobiology. Pathology Unit | Hill Marcelo, Institut Pasteur de Montevideo (Uruguay). Laboratory of Immunoregulation and Inflammation / Universidad de la República (Uruguay). Faculty of Medicine. Immunobiology Department | Verdes García José Manuel, Universidad de la República (Uruguay). Veterinary Faculty. Department of Pathobiology. Pathology Unit | Duhalde Vega Maite, Institut Pasteur de Montevideo (Uruguay). Laboratory of Immunoregulation and Inflammation / University of Buenos Aires (Buenos Aires, Argentina). School of Pharmacy and Biochemistry. Institute of Biological Chemistry and Chemical Physics (UBA‑CONICET) | Bollati-Fogolín Mariela, Institut Pasteur de Montevideo (Uruguay). Cell Biology Unit | Crispo Martina, Institut Pasteur de Montevideo (Uruguay). Transgenic and Experimental Animal Unit
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.
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