Antiviral Research ( IF 4.5 ) Pub Date : 2022-10-15 , DOI: 10.1016/j.antiviral.2022.105433 Leah V Goulding 1 , Eleonóra Kiss 2 , Lynnette Goatley 1 , Robert Vrancken 2 , Nesya E J Goris 2 , Linda Dixon 1
African swine fever virus (ASFV) causes a haemorrhagic disease affecting wild boar and domestic pigs which can result in morbidity and fatality rates of up to 100%. ASFV is a large double-stranded DNA virus which replicates predominantly in the cell cytoplasm and codes for its replication and transcription machinery. No vaccine is widely available and control depends on early detection, culling of infected herds and adherence to biosecurity measures. In this study the small molecule nucleoside analogue, cyclic cidofovir (cHPMPC), was evaluated for its ability to inhibit replication of four different ASFV genotypes in primary porcine macrophages. Time of addition studies demonstrated that cHPMPC effectively inhibits ASFV replication and late gene expression when added pre-infection or early post-infection but not when added at late times, suggesting the drug target may be the virus DNA polymerase, or the RNA polymerase involved in late transcription. Oral administration of cHPMPC delayed onset of clinical signs and significantly reduced viral titres in blood and tissues of treated pigs. These results indicate that cHPMPC is a promising compound for further development to control ASFV outbreaks.
中文翻译:
核苷类似物 cHPMPC 对非洲猪瘟病毒复制的体外和体内抗病毒活性
非洲猪瘟病毒 (ASFV) 引起一种影响野猪和家猪的出血性疾病,可导致高达 100% 的发病率和死亡率。ASFV 是一种大型双链 DNA 病毒,主要在细胞质中复制,并编码其复制和转录机制。没有疫苗可以广泛使用,控制取决于早期发现、扑杀受感染的牛群和遵守生物安全措施。在这项研究中,评估了小分子核苷类似物环状西多福韦 (cHPMPC) 抑制原代猪巨噬细胞中四种不同 ASFV 基因型复制的能力。添加时间研究表明,在感染前或感染后早期添加时,cHPMPC 可有效抑制 ASFV 复制和晚期基因表达,但在后期添加时则无效,表明药物靶标可能是病毒DNA聚合酶,或参与后期转录的RNA聚合酶。口服 cHPMPC 可延迟临床症状的出现,并显着降低治疗猪血液和组织中的病毒滴度。这些结果表明,cHPMPC 是一种很有前途的化合物,可以进一步开发以控制 ASFV 爆发。