Ivermectin reduces in vivo coronavirus infection in a mouse experimental model

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.

Attenuation of clinical and immunological outcomes during SARS‐CoV‐2 infection by ivermectin

“…This effect may be related to a modulation of the inflammatory response in the lung (downregulation of Tnf‐α in males, Tnfaip3 in both sexes, and Il‐6 in females) associated with reduced clinical signs. Tnf‐α reduction and better clinical presentation are common features caused by the IVM treatment in another model of coronavirus infection, where mice were infected with MHV (Arévalo et al , 2021 ). Additionally, differently from the nasal turbinates, the Il‐6/Il‐10 ratio in the lung of IVM‐treated hamsters was significantly lower than in non‐treated animals (Fig 2B ), which may relate to their comparatively better clinical presentation.…”

“…IVM has been shown to be active beyond its anti‐parasitic activity in a wide variety of pathologies, including cancer, allergy, and viral infections (Laing et al , 2017 ). Recently, IVM has been reported to reduce viral load and improve the clinical status of mice infected by an animal coronavirus, the mouse hepatitis virus (MHV) (Arévalo et al , 2021 ). In vitro inhibition of SARS‐CoV‐2 replication by IVM in Vero/hSLAM cells has also been reported (Caly et al , 2020 ), albeit at much higher concentrations (50‐ to 100‐fold) than those clinically attainable in humans (150–400 µg/kg) (Guzzo et al , 2002 ; Bray et al , 2020 ; Chaccour et al , 2020 ).…”

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

“…Certain in vivo findings suggest that the main activity of IVM against SARS-CoV-2 may apply to viral morbidity rather than infectivity, consistent with its main underlying biological mechanism being competitive inhibition of viral binding to host glycans. Two animal studies of IVM treatment at low human-equivalent doses, one for the SARS-CoV-2 virus in golden hamsters [ 215 ] and another for a related betacoronavirus (MHV-A59) in mice [ 216 ], found statistically significant treatment reductions in morbidities but either no reduction or a lesser reduction, respectively, in viral load. Some RCTs for IVM treatment of COVID-19 have found no reductions in viral load for most patients [ 217 ], or at most insignificant reductions in viral load accompanied by significant reductions in mortality [ 218 ] or symptoms [ 219 ] for the treatment groups.…”

Nanoceria Can Inhibit the Reproduction of Transmissible Gastroenteritis Virus: Consideration for Use to Prevent and Treat Coronavirus Disease

“…The next step includes in vivo tests using mouse models, e.g., as in [11]. Development of nanoceria-based drugs, and composites of nanoceria with effective substances (like fenugreek, curcumin, etc.)…”