Ivermectin reduces in vivo coronavirus infection in a mouse experimental model

• Published in: Scientific reports Vol. 11; no. 1; p. 7132
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.03.2021; Nature Publishing Group; Nature Portfolio
• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-86679-0

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.