Department of Virology, Bursa Uludag University, Faculty of Veterinary Medicine, 16059, Bursa, Turkey.
Department of Virology, Bursa Uludag University, Faculty of Veterinary Medicine, 16059, Bursa, Turkey.
Virus Res. 2021 May;297:198384. doi: 10.1016/j.virusres.2021.198384. Epub 2021 Mar 10.
Bovine respiratory disease (BRD) complex is an important viral infection that causes huge economic losses in cattle herds worldwide. However, there is no directly effective antiviral drug application against respiratory viral pathogens; generally, the metaphylactic antibacterial drug applications are used for BRD. Ivermectin (IVM) is currently used as a broad-spectrum anti-parasitic agent both for veterinary and human medicine on some occasions. Moreover, since it is identified as an inhibitor for importin α/β-mediated nuclear localization signal (NLS), IVM is also reported to have antiviral potential against several RNA and DNA viruses. Since therapeutic use of IVM in COVID-19 cases has recently been postulated, the potential antiviral activity of IVM against bovine respiratory viruses including BRSV, BPIV-3, BoHV-1, BCoV and BVDV are evaluated in this study. For these purposes, virus titration assay was used to evaluate titers in viral harvest from infected cells treated with non-cytotoxic IVM concentrations (1, 2.5 and 5 μM) and compared to titers from non-treated infected cells. This study indicated that IVM inhibits the replication of BCoV, BVDV, BRSV, BPIV-3 and BoHV-1 in a dose-dependent manner in vitro as well as number of extracellular infectious virions. In addition, it was demonstrated that IVM has no clear effect on the attachment and penetration steps of the replication of the studied viruses. Finally, this study shows for the first time that IVM can inhibit infection of BRD-related viral agents namely BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM. Consequently, IVM, which is licensed for antiparasitic indications, also deserves to be evaluated as a broad-spectrum antiviral in BRD cases caused by viral pathogens.
牛呼吸道疾病(BRD)复合体是一种重要的病毒性感染,在全球牛群中造成巨大的经济损失。然而,目前还没有针对呼吸道病毒病原体的直接有效抗病毒药物应用;通常,针对 BRD 会使用预防性抗菌药物。伊维菌素(IVM)目前在兽医和人类医学中都被用作广谱抗寄生虫药物。此外,由于它被鉴定为抑制进口蛋白 α/β介导的核定位信号(NLS)的物质,因此 IVM 也被报道具有针对几种 RNA 和 DNA 病毒的抗病毒潜力。由于最近有人提出在 COVID-19 病例中使用 IVM 的治疗用途,因此本研究评估了 IVM 对包括牛呼吸道合胞体病毒(BRSV)、牛副流感病毒-3 型(BPIV-3)、牛疱疹病毒-1 型(BoHV-1)、牛冠状病毒(BCoV)和牛病毒性腹泻病毒(BVDV)在内的牛呼吸道病毒的潜在抗病毒活性。为此,使用病毒滴定测定法评估了在非细胞毒性 IVM 浓度(1、2.5 和 5 μM)处理的感染细胞中病毒收获物的滴度,并与未经处理的感染细胞的滴度进行了比较。这项研究表明,IVM 以剂量依赖的方式在体外抑制 BCoV、BVDV、BRSV、BPIV-3 和 BoHV-1 的复制,也减少了细胞外传染性病毒粒子的数量。此外,研究表明 IVM 对研究病毒复制的附着和穿透步骤没有明显影响。最后,本研究首次表明,IVM 可以在 2.5 和 5 μM 的浓度下抑制 BRD 相关病毒制剂,即 BCoV、BPIV-3、BVDV、BRSV 和 BoHV-1 的感染。因此,伊维菌素(IVM),作为一种已获得抗寄生虫适应症的药物,也值得在由病毒病原体引起的 BRD 病例中作为广谱抗病毒药物进行评估。