In Vitro effects of antiviral activity and some cytokine levels of Ivermectin on cells infected with BCoV

Bovine coronavirus (BCoV) is a significant viral pathogen responsible for enteric and respiratory diseases in cattle. Due to its association with various animal diseases and its close relation to human coronaviruses, BCoV has attracted considerable attention from both cattle producers and researchers. Currently, effective antiviral treatment options for controlling BCoV infections are limited. This study aimed to evaluate the antiviral activity of Ivermectin (IVM) against BCoV-infected Madin-Darby Bovine Kidney (MDBK) cells, as well as its immunomodulatory effects on cytokines including Tumor Necrosis Factor-α (TNF-α), Interferon Regulatory Factor 3 (IRF-3), Interferon-γ (IFN-γ), Nuclear Factor kappa B (NF-κB), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Interferon-β (IFN-β), and Interleukin-8 (IL-8) in vitro. Additionally, based on the obtained data, comparative analyses of gene expression levels among experimental groups—cell control (CC), virus control (VC), substance control (SC), and IVM+BCoV—were conducted to elucidate the functional roles of cytokines secreted or inhibited in the cell lines. Initially, the antiviral efficacy of a non-cytotoxic concentration of IVM (5 µM) against BCoV attachment and replication stages was assessed via titration assays. Furthermore, the immunomodulatory effects of IVM on the aforementioned cytokine levels in BCoV-infected cells were examined using real-time quantitative Polymerase Chain Reaction (real-time qPCR) employing the 2^-ΔΔCt method. In this study, Ivermectin (IVM) was found to inhibit Bovine Coronavirus (BCoV) replication by an average of 95.6% and to modulate the immune response, particularly by regulating the proinflammatory cytokines IL-8 and IL-1β. The fold changes in cellular gene expression levels varied considerably among all experimental groups depending on both the time points and the comparison groups. Overall, the findings suggest that this study may serve as a foundation for future in vivo and clinical research, and that IVM could potentially contribute to the development of therapeutic strategies against BCoV infections as an antiviral and/or immunomodulatory agent.