Hycanthone inhibits African swine fever virus replication by inhibiting the cellular AKTphosphorylation and inducing viral DNA damage in porcine alveolar macrophage cultures

IF 6.5 3区农林科学 Q1 VETERINARY SCIENCES

Pakistan Veterinary Journal Pub Date : 2025-01-01 DOI:10.29261/pakvetj/2025.228

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引用次数: 0

Abstract

African swine fever (ASF), caused by ASF virus (ASFV) infection, is a highly contagious and severe hemorrhagic viral disease with significant economic implications for the global pig farming industry.Currently, there are no effective vaccines or antiviral drugs available for controlling ASF epidemics.Developing effective strategies to combat this epidemic has become imperative.In this study, by screening a chemical library with 400 small molecule compounds, we identified that hycanthone, a previously used anthelminthic drug, exhibits the most potent inhibition on ASFV replication in PAMs, with an IC50 value of 0.57 mol/L.Hycanthone showed dose-dependent antiviral activity, reducing the mRNA levels of ASFV p30 and p72 proteins and decreasing viral DNA synthesis.Mechanistically, hycanthone attenuates ASFV replication by suppressing the cellular AKT phosphorylation and inducing viral DNA damage through interacting with ASFV AP endonuclease.Our findings suggest that hycanthone could serve as a promising therapeutic candidate for controlling ASFV infections.

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在猪肺泡巨噬细胞培养中，海坎索酮通过抑制细胞akt磷酸化和诱导病毒DNA损伤来抑制非洲猪瘟病毒复制

非洲猪瘟（ASF）由非洲猪瘟病毒（ASFV）感染引起，是一种高度传染性和严重出血性病毒性疾病，对全球养猪业具有重大经济影响。目前，还没有有效的疫苗或抗病毒药物来控制非洲猪瘟的流行。制定防治这一流行病的有效战略已成为当务之急。在本研究中，通过筛选400个小分子化合物的化学文库，我们发现hycanthone，一种以前使用的抗虫药物，在PAMs中表现出最有效的抑制ASFV复制，IC50值为0.57 mol/L。海果酮显示出剂量依赖性抗病毒活性，降低ASFV p30和p72蛋白mRNA水平，并降低病毒DNA合成。机制上，海甘松通过抑制细胞AKT磷酸化，并通过与ASFV AP内切酶相互作用诱导病毒DNA损伤，从而减弱ASFV的复制。我们的研究结果表明，hycanthone可以作为控制ASFV感染的有希望的治疗候选药物。

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来源期刊

Pakistan Veterinary Journal 兽医-兽医学

CiteScore

4.20

自引率

13.00%

发文量

审稿时长

4-8 weeks

期刊介绍： The Pakistan Veterinary Journal (Pak Vet J), a quarterly publication, is being published regularly since 1981 by the Faculty of Veterinary Science, University of Agriculture, Faisalabad, Pakistan. It publishes original research manuscripts and review articles on health and diseases of animals including its various aspects like pathology, microbiology, pharmacology, parasitology and its treatment. The “Pak Vet J” (www.pvj.com.pk) is included in Science Citation Index Expended and has got 1.217 impact factor in JCR 2017. Among Veterinary Science Journals of the world (136), “Pak Vet J” has been i) ranked at 75th position and ii) placed Q2 in Quartile in Category. The journal is read, abstracted and indexed internationally.