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Antiviral research. 2025 Apr 2:106155. doi: 10.1016/j.antiviral.2025.106155 Q14.52024

Salicylamide derivative JMX0312 protects immunosuppressed Syrian hamsters against adenovirus lethal challenge

唾洛氯amide衍生物JMX0312能够保护免疫抑制的叙利亚地鼠免受腺病毒致死性攻击 翻译改进

Carretero-Ledesma Marta  1, Jun Li  2, Martín-Escolano Javier  1, Herrera-Espejo Soraya  1, Jimin Xu  2, Haiying Chen  2, Díaz-Navarro Caridad  3, Jerónimo Pachón  4, Sánchez-Céspedes Javier  5, Jia Zhou  6, Pachón-Ibáñez María Eugenia  7

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作者单位

  • 1 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain.
  • 2 Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
  • 3 MEDINA Foundation Center of Excellence in Innovative Medicines Research in Andalusia, 18016, Granada, Spain.
  • 4 Division of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, 41013, Spain; Department of Medicine, School of Medicine, University of Seville, Seville, Spain.
  • 5 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Division of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, 41013, Spain; CIBERINFEC, ISCIII - CIBER of Infectious Diseases, The Institute of Health Carlos III (ISCIII), Madrid, Spain. Electronic address: jsanchez-ibis@us.es.
  • 6 Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA. Electronic address: jizhou@utmb.edu.
  • 7 Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Division of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, 41013, Spain; CIBERINFEC, ISCIII - CIBER of Infectious Diseases, The Institute of Health Carlos III (ISCIII), Madrid, Spain.
  • DOI: 10.1016/j.antiviral.2025.106155 PMID: 40185285

    摘要 中英对照阅读

    Despite the fact that human adenovirus (HAdV) causes severe infections in immunosuppressed and immunocompetent individuals, especially in children, there is currently no specific treatment for these infections. Previously we reported a new salicylamide analogue, JMX0312, as a potent inhibitor of HAdV infection with low cytotoxicity in vitro. Here we evaluate the in vivo efficacy and safety of this molecule in the immunosuppressed Syrian hamster model of HAdV infection. JMX0312 administration at a dose of 6.25 mg/kg did not affect the body weight of the animals, and reduced the viral load in liver and blood in a similar way than cidofovir. Also, JMX0312 reduced the mortality of the animals, although in a lesser extent than cidofovir, a drug used to treat these infections that must be subject to rigorous monitoring due to its high toxicity and whose used is not approved in children. Our findings highlight the potential of this new antiviral agent for the treatment of HAdV infections, paving the way for future pre-clinical and clinical trial development towards a safer and more effective treatment against HAdV-associated infections.

    Keywords: Adenovirus; Antiviral drugs; Immunosuppression; JMX0312; Niclosamide; Syrian hamster.

    Keywords:salicylamide derivative; immunosuppressed hamsters; adenovirus challenge

    尽管人腺病毒(HAdV)可导致免疫抑制和免疫功能正常个体,尤其是儿童的严重感染,但目前尚无针对这些感染的具体治疗方法。此前我们报道了一种新的水杨酰胺类似物JMX0312,在体外实验中表现出对HAdV感染的强大抑制作用且细胞毒性较低。本文评估了该分子在免疫抑制叙利亚仓鼠模型中的体内疗效和安全性。

    给予6.25 mg/kg剂量的JMX0312并未影响动物体重,并以与cidofovir相似的方式降低了肝脏和血液中的病毒载量。此外,JMX0312还减少了动物死亡率,尽管其效果略逊于cidofovir(用于治疗这些感染的一种药物),由于其高毒性,该药物的使用必须受到严格监控,在儿童中也未被批准使用。

    我们的研究结果突显了这种新型抗病毒剂在HAdV感染治疗中的潜力,并为未来临床前和临床试验的发展铺平道路,从而寻求更安全、更有效的针对与HAdV相关感染的治疗方法。

    关键词:腺病毒;抗病毒药物;免疫抑制;JMX0312;尼克洛胺;叙利亚仓鼠。

    版权 © 2025. 出版社:Elsevier B.V.

    关键词:水杨酰胺衍生物; 免疫抑制仓鼠; 腺病毒攻击

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    期刊名:Antiviral research

    缩写:ANTIVIR RES

    ISSN:0166-3542

    e-ISSN:1872-9096

    IF/分区:4.5/Q1

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    Salicylamide derivative JMX0312 protects immunosuppressed Syrian hamsters against adenovirus lethal challenge