传染性造血系统坏死病毒(IHNV)在全球范围内引起传染性造血系统坏死和鲑鱼和鳟鱼养殖的严重经济损失。目前,针对IHNV的唯一商业疫苗是具有一些生物安全性问题的DNA疫苗。因此,需要更有效的疫苗和抗病毒药物来预防IHNV感染。在这项研究中,从中药单体库中筛选出1483个化合物,和bufalin显示出针对IHNV的潜在抗病毒活性。Bufalin的50%细胞毒性浓度>20µM,并且对IHNV的50%抑制浓度为0.1223μΜ。Bufalin在体外显示出对多种IHNV菌株的抑制作用,这证实了它对所有IHNV菌株都有抑制作用,而不是针对单一菌株的随机活动。Bufalin介导的IHNV感染阻断发生在病毒附着和RNA复制阶段,但不是内在化。与模拟药物治疗组相比,Bufalin还抑制了体内IHNV感染,并显着增加了虹鳟鱼的存活率,这通过体内病毒载量监测得到证实。我们的数据表明,蟾蜍灵的抗IHNV活性与细胞外Na浓度成正比,与细胞外K浓度成反比,蟾蜍灵可通过靶向Na+/K+-ATP酶抑制IHNV感染。体外和体内研究表明,蟾蜍灵显着抑制IHNV感染,可能是虹鳟鱼中一种有前途的候选药物。重要传染性造血坏死病毒(IHNV)是传染性造血坏死病毒(IHN)的病原体,其暴发常常造成巨大的经济损失,阻碍鲑鱼和鳟鱼养殖的健康发展。目前,全世界只有一种被批准用于IHN的DNA疫苗,但它面临一些生物安全问题。因此,需要更有效的疫苗和抗病毒药物来预防IHNV感染。在这项研究中,我们报告说布法林,中药,在体外和体内均显示针对IHNV的潜在抗病毒活性。Bufalin介导的IHNV感染阻断发生在病毒附着和RNA复制阶段,但不是内在化,蟾蜍灵通过靶向Na+/K+-ATP酶抑制IHNV感染。体外和体内研究表明,蟾蜍灵显着抑制IHNV感染,可能是虹鳟鱼中一种有前途的候选药物。
Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis and severe economic losses to salmon and trout aquaculture worldwide. Currently, the only commercial vaccine against IHNV is a DNA vaccine with some biosafety concerns. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, 1,483 compounds were screened from a traditional Chinese medicine monomer library, and bufalin showed potential antiviral activity against IHNV. The 50% cytotoxic concentration of bufalin was >20 µM, and the 50% inhibitory concentration was 0.1223 µΜ against IHNV. Bufalin showed the inhibition of diverse IHNV strains in vitro, which confirmed that it had an inhibitory effect against all IHNV strains, rather than random activity against a single strain. The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization. Bufalin also inhibited IHNV infection in vivo and significantly increased the survival of rainbow trout compared with the mock drug-treated group, and this was confirmed by in vivo viral load monitoring. Our data showed that the anti-IHNV activity of bufalin was proportional to extracellular Na+ concentration and inversely proportional to extracellular K+ concentration, and bufalin may inhibit IHNV infection by targeting Na+/K+-ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout.
OBJECTIVE: Infectious hematopoietic necrosis virus (IHNV) is the pathogen of infectious hematopoietic necrosis (IHN) which outbreak often causes huge economic losses and hampers the healthy development of salmon and trout farming. Currently, there is only one approved DNA vaccine for IHN worldwide, but it faces some biosafety problems. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, we report that bufalin, a traditional Chinese medicine, shows potential antiviral activity against IHNV both in vitro and in vivo. The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization, and bufalin inhibited IHNV infection by targeting Na+/K+-ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout.