دورية أكاديمية
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Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.

التفاصيل البيبلوغرافية
العنوان: Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.
المؤلفون: Wang T; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Zheng G; School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China., Chen Z; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Wang Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Zhao C; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Li Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Yuan Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China., Duan H; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Agricultural University, Zhengzhou, Henan 450046, China., Zhu H; School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China., Yang X; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Agricultural University, Zhengzhou, Henan 450046, China., Li W; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China., Du W; Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584CL, the Netherlands., Li Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Agricultural University, Zhengzhou, Henan 450046, China. Electronic address: yongtaole@126.com., Li D; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Agricultural University, Zhengzhou, Henan 450046, China. Electronic address: 497222038@sina.com.
المصدر: Virus research [Virus Res] 2024 Jan 02; Vol. 339, pp. 199275. Date of Electronic Publication: 2023 Nov 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8410979 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7492 (Electronic) Linking ISSN: 01681702 NLM ISO Abbreviation: Virus Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier Science, c1984-
مواضيع طبية MeSH: Nidovirales* , Coronavirus* , Coronavirus Infections* , Porcine epidemic diarrhea virus*/genetics , Swine Diseases*, Chlorocebus aethiops ; Humans ; Animals ; Swine ; Vero Cells ; Tubercidin/pharmacology ; Tubercidin/therapeutic use ; Drug Repositioning ; Molecular Docking Simulation ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use
مستخلص: The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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فهرسة مساهمة: Keywords: Antiviral; Coronavirus; Porcine epidemic diarrhea virus; RNA-dependent RNA polymerase; Tubercidin
المشرفين على المادة: M351LCX45Y (Tubercidin)
0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20231126 Date Completed: 20231216 Latest Revision: 20240520
رمز التحديث: 20240520
مُعرف محوري في PubMed: PMC10730850
DOI: 10.1016/j.virusres.2023.199275
PMID: 38008220
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-7492
DOI:10.1016/j.virusres.2023.199275