de León Patricia, Bustos María José, Torres Elisa, Cañas-Arranz Rodrigo, Sobrino Francisco, Carrascosa Angel L
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
Front Microbiol. 2019 Aug 14;10:1853. doi: 10.3389/fmicb.2019.01853. eCollection 2019.
Antiviral compounds targeting cellular metabolism instead of virus components have become an interesting issue for preventing and controlling the spread of virus infection, either as sole treatment or as a complement of vaccination. Some of these compounds are involved in the control of lipid metabolism and/or membrane rearrangements. Here, we describe the effect of three of these cell-targeting antivirals: lauryl gallate (LG), valproic acid (VPA), and cerulenin (CRL) in the multiplication of viruses causing important porcine diseases. The results confirm the antiviral action in cultured cells of LG against African swine fever virus (ASFV), foot and mouth disease virus (FMDV), vesicular stomatitis virus (VSV), and swine vesicular disease virus (SVDV), as well as the inhibitory effect of VPA and CRL on ASFV infection. Other gallate esters have been also assayed for their inhibition of FMDV growth. The combined action of these antivirals has been also tested in ASFV infections, with some synergistic effects when LG and VPA were co-administered. Regarding the mode of action of the antivirals, experiments on the effect of the time of its addition in infected cell cultures indicated that the inhibition by VPA and CRL occurred at early times after ASFV infection, while LG inhibited a late step in FMDV infection. In all the cases, the presence of the antiviral reduced or abolished the induction of virus-specific proteins. Interestingly, LG also reduced mortality and FMDV load in a mouse model. The possible use of cell-targeted antivirals against porcine diseases is discussed.
靶向细胞代谢而非病毒成分的抗病毒化合物已成为预防和控制病毒感染传播的一个有趣课题,可作为单一治疗方法或作为疫苗接种的补充。其中一些化合物参与脂质代谢的控制和/或膜重排。在这里,我们描述了三种靶向细胞的抗病毒药物:没食子酸月桂酯(LG)、丙戊酸(VPA)和浅蓝菌素(CRL)对引起重要猪病的病毒增殖的影响。结果证实了LG在培养细胞中对非洲猪瘟病毒(ASFV)、口蹄疫病毒(FMDV)、水疱性口炎病毒(VSV)和猪水疱病病毒(SVDV)的抗病毒作用,以及VPA和CRL对ASFV感染的抑制作用。还检测了其他没食子酸酯对FMDV生长的抑制作用。这些抗病毒药物的联合作用也在ASFV感染中进行了测试,当LG和VPA联合使用时具有一些协同作用。关于抗病毒药物的作用方式,在感染细胞培养物中添加药物时间的影响实验表明,VPA和CRL的抑制作用发生在ASFV感染后的早期,而LG抑制FMDV感染的后期步骤。在所有情况下,抗病毒药物的存在降低或消除了病毒特异性蛋白的诱导。有趣的是,LG还降低了小鼠模型中的死亡率和FMDV载量。本文讨论了靶向细胞的抗病毒药物在猪病治疗中的潜在应用。