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抗病毒药物T-1105的施用能使猪完全免受口蹄疫感染。

Administration of the antiviral agent T-1105 fully protects pigs from foot-and-mouth disease infection.

作者信息

Nishi Tatsuya, Fukai Katsuhiko, Masujin Kentaro, Kawaguchi Rie, Ikezawa Mitsutaka, Yamada Manabu, Nakajima Nozomi, Komeno Takashi, Furuta Yousuke, Sugihara Hiromi, Kurosaki Chie, Sakamoto Kenichi, Morioka Kazuki

机构信息

Kodaira Research Station, National Institute of Animal Health, National Agriculture and Food Research Organization, 6-20-1, Josui-honcho, Kodaira, Tokyo, 187-0022, Japan.

Division of Pathology and Pathophysiology, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5, Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.

出版信息

Antiviral Res. 2022 Dec;208:105425. doi: 10.1016/j.antiviral.2022.105425. Epub 2022 Sep 28.

Abstract

Foot-and-mouth disease (FMD) is a contagious disease affecting cloven-hoofed animals. Its transmissibility and antigenic variety make this disease difficult to control. Antiviral agents are expected to have an immediate effect that is independent of viral antigenicity; thus, they can serve as effective tools for inhibiting the spread of the causative agent, the FMD virus (FMDV), from infected animals. In this study, we investigated the antiviral activity of a pyrazinecarboxamide derivative, T-1105, against FMDV. Cytopathic effect inhibition assays revealed that T-1105 strongly inhibited the replication of 28 reference strains of all seven FMDV serotypes at non-cytotoxic concentrations. The antiviral effect of T-1105 against FMDV was also evaluated by experimental infection of domestic pigs. T-1105 was administered orally to pigs starting 1 h before or 6 h after the inoculation of a porcinophilic FMDV serotype O, topotype CATHAY. None of the pigs administered with T-1105 showed clinical signs of FMD. Moreover, no infectious FMDVs or FMDV-specific genes were detected in their sera, oral and nasal discharges, or tissues collected 48 h after virus inoculation. These findings strongly suggest that administration of T-1105 is effective in controlling the spread of FMDV in pigs.

摘要

口蹄疫(FMD)是一种影响偶蹄动物的传染病。其传播性和抗原多样性使得这种疾病难以控制。抗病毒药物有望产生与病毒抗原性无关的即时效果;因此,它们可作为抑制病原体口蹄疫病毒(FMDV)从受感染动物传播的有效工具。在本研究中,我们研究了吡嗪甲酰胺衍生物T-1105对FMDV的抗病毒活性。细胞病变效应抑制试验表明,T-1105在无细胞毒性浓度下强烈抑制所有七种FMDV血清型的28种参考毒株的复制。还通过对家猪进行实验性感染来评估T-1105对FMDV的抗病毒效果。在接种嗜猪型FMDV血清型O、CATHAY拓扑型之前1小时或之后6小时开始给猪口服T-1105。接受T-1105治疗的猪均未出现口蹄疫的临床症状。此外,在病毒接种后48小时采集的血清、口腔和鼻腔分泌物或组织中未检测到传染性FMDV或FMDV特异性基因。这些发现有力地表明,给予T-1105可有效控制FMDV在猪中的传播。

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