MK-0608 inhibits in vitro and in vivo RNA replication of infectious pancreatic necrosis virus
文献类型： 外文期刊
作者： Li, Linfang 1 ; Zhao, Jingzhuang 2 ; Shao, Yizhi 2 ; Ma, Jie 4 ; Lu, Tongyan 2 ; Xu, Liming 2 ;
作者机构： 1.Univ Shanghai Ocean Univ, Coll Fisheries & Life Sci, Shanghai, Peoples R China
2.Chinese Acad Fishery Sci, Heilongjiang River Fisheries Res Inst, Dept Aquatic Anim Dis & Control, Harbin, Peoples R China
3.Key Lab Aquatic Anim Dis & Immune Technol Heilongj, Harbin, Peoples R China
4.Univ Idaho, Dept Fish & Wildlife Sci, Moscow, ID USA
关键词： MK-0608; Antiviral compound; IPNV; RdRp; Rainbow trout
期刊名称：FISH & SHELLFISH IMMUNOLOGY （ 影响因子：4.1； 五年影响因子：4.2 ）
ISSN： 1050-4648
年卷期： 2024 年 151 卷
页码：
收录情况： SCI
摘要： Infectious pancreatic necrosis virus (IPNV) is an important pathogen that is threatening the worldwide salmon and trout industry. But there is no therapeutic drug available for now. In this study, we demonstrate that MK0608 is highly efficient against IPNV and low cytotoxic, with a 50 % effective concentration (EC50) of 0.20 mu M and selectivity index (SI) of about 268. Time of addition assay illustrated that MK-0608 targeted the early stage of IPNV life cycle. Furthermore, we found that MK-0608 blocked IPNV attachment on the premise of sufficient pre-incubation time but MK-0608 did not influence viral internalization and release. MK-0608 could inhibit IPNV genome synthesis, and combination with ribavirin enhanced the inhibition effect, which might be functional via binding to IPNV RNA dependent RNA polymerase (RdRp), which was predicted by using molecular docking methods. In vivo test showed that IPNV was extremely suppressed in the rainbow trout (Oncorhynchus mykiss) with one single dose of MK-0608, and the higher dosage of 50 mg/kg could cause 3 log decrease of IPNV loads in fish tissues.
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