Lack of antiviral activity of ivermectin against foot-and-mouth disease virus serotype O in BALB/c mice

Sheeza Arshad; Sohail Raza; Rehan Rafique; Imran Altaf; Adeel Sattar

doi:10.1016/j.micpath.2023.106245

Lack of antiviral activity of ivermectin against foot-and-mouth disease virus serotype O in BALB/c mice

Microb Pathog. 2023 Sep:182:106245. doi: 10.1016/j.micpath.2023.106245. Epub 2023 Jul 6.

Authors

Sheeza Arshad¹, Sohail Raza², Rehan Rafique³, Imran Altaf¹, Adeel Sattar⁴

Affiliations

¹ Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
² Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan. Electronic address: sohail.raza@uvas.edu.pk.
³ Foot-and-mouth disease Research Center, Lahore, Pakistan.
⁴ Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

PMID: 37422171
DOI: 10.1016/j.micpath.2023.106245

Abstract

Ivermectin is an FDA approved drug and showed in vitro antiviral activity against different serotypes of Foot-and-mouth disease virus (FMDV). We here assessed the effect of ivermectin in 12 day old female BALB/c mice infected with 50LD₅₀ FMDV serotype O intraperitoneally. Initially FMDV was adopted on 3-day old BALB/c mice by blind passages. After successful adaptation of virus mice showed hind limb paralysis. Mice were divided in 6 different groups and each group has 6 mice. Ivermectin was given at clinically prescribed dose of 500 μg/kg subcutaneously at different time interval. Ivermectin was given at 0 h post infection (hpi) and 12 hpi. Moreover we compared commercially available ivermectin with purified ivermectin preparation in sterilized DMSO. Viral load was evaluated through RT-qPCR and ELISA in different groups. Results showed that positive control and negative control has CT-value 26.28 and 38 respectively. Treated groups at 0hpi, 12hpi, purified ivermectin and pre-post treatment group has CT values 24.89, 29.44, 27.26 and 26.69 respectively that showed there was no significant reduction in virus load in treated groups as compare to positive control. In histopathology of lung tissue perialveolar capillaries were congested and alveoli were altelactic. Some emphysema was seen in alveoli and mild thickening in the alveolar wall was observed. In the alveolar epithelium mononuclear cells infiltration was seen. There was discoloration haemorrhages and enlargement of heart. Degeneration, fragmentation and loss of sarcoplasm were seen in the cardiac muscle fibers. Above results showed that ivermectin did not lessen lung and heart viral load. This study contributes that ivermectin does not have a significant antiviral effect when used in mice against FMDV serotype O, according to a growing body of research.

Keywords: Antiviral; BALB/C; Foot-and-mouth disease virus; In vivo; Ivermectin.