关键词: Antiviral drug Double membrane vesicles K22 Nidoviruses Replication organelles

Mesh : Animals Antiviral Agents / pharmacology Arterivirus / drug effects genetics growth & development metabolism Benzamides / pharmacology Carps Cell Line Chlorocebus aethiops Coronaviridae / drug effects genetics growth & development metabolism Epithelial Cells / drug effects virology Equartevirus / drug effects genetics growth & development metabolism Mesocricetus Piperidines / pharmacology Porcine respiratory and reproductive syndrome virus / drug effects genetics growth & development metabolism RNA, Double-Stranded / antagonists & inhibitors biosynthesis genetics RNA, Viral / antagonists & inhibitors biosynthesis genetics Torovirus / drug effects genetics growth & development metabolism Virus Replication / drug effects

来  源:   DOI:10.1016/j.virusres.2018.01.002

Abstract:
Recently, a novel antiviral compound (K22) that inhibits replication of a broad range of animal and human coronaviruses was reported to interfere with viral RNA synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al., 2014). Here we assessed potential antiviral activities of K22 against a range of viruses representing two (sub)families of the order Nidovirales, the Arteriviridae (porcine reproductive and respiratory syndrome virus [PRRSV], equine arteritis virus [EAV] and simian hemorrhagic fever virus [SHFV]), and the Torovirinae (equine torovirus [EToV] and White Bream virus [WBV]). Possible effects of K22 on nidovirus replication were studied in suitable cell lines. K22 concentrations significantly decreasing infectious titres of the viruses included in this study ranged from 25 to 50 μM. Reduction of double-stranded RNA intermediates of viral replication in nidovirus-infected cells treated with K22 confirmed the anti-viral potential of K22. Collectively, the data show that K22 has antiviral activity against diverse lineages of nidoviruses, suggesting that the inhibitor targets a critical and conserved step during nidovirus replication.
摘要:
最近,据报道,一种抑制多种动物和人冠状病毒复制的新型抗病毒化合物(K22)通过损害双膜囊泡(DMV)形成而干扰病毒RNA合成(Lundin等.,2014).在这里,我们评估了K22对代表Nidovirales的两个(亚)家族的一系列病毒的潜在抗病毒活性,动脉炎病毒科(猪繁殖与呼吸综合征病毒[PRRSV],马动脉炎病毒[EAV]和猿猴出血热病毒[SHFV]),和Torovirinae(马圆环病毒[EToV]和白Bream病毒[WBV])。在合适的细胞系中研究了K22对nidovirus复制的可能影响。显著降低本研究中包括的病毒的感染滴度的K22浓度范围为25至50μM。用K22处理的nidovirus感染的细胞中病毒复制的双链RNA中间体的减少证实了K22的抗病毒潜力。总的来说,数据显示,K22对多种病毒谱系具有抗病毒活性,表明该抑制剂靶向nidovirus复制过程中的关键和保守步骤.
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