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Naturally Derived Terpenoids Targeting the 3D pol of Foot-and-Mouth Disease Virus: An Integrated In Silico and In Vitro Investigation.

التفاصيل البيبلوغرافية
العنوان: Naturally Derived Terpenoids Targeting the 3D pol of Foot-and-Mouth Disease Virus: An Integrated In Silico and In Vitro Investigation.
المؤلفون: Mana N; Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Theerawatanasirikul S; Department of Anatomy, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Semkum P; Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Lekcharoensuk P; Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.
المصدر: Viruses [Viruses] 2024 Jul 14; Vol. 16 (7). Date of Electronic Publication: 2024 Jul 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Foot-and-Mouth Disease Virus*/drug effects , Antiviral Agents*/pharmacology , Antiviral Agents*/chemistry , Terpenes*/pharmacology , Terpenes*/chemistry, Animals ; Cell Line ; Virus Replication/drug effects ; Computer Simulation ; RNA-Dependent RNA Polymerase/metabolism ; RNA-Dependent RNA Polymerase/antagonists & inhibitors ; Cricetinae ; Molecular Docking Simulation ; Foot-and-Mouth Disease/virology ; Foot-and-Mouth Disease/drug therapy ; Diterpenes/pharmacology ; Diterpenes/chemistry
مستخلص: Foot-and-mouth disease virus (FMDV) belongs to the Picornaviridae family and is an important pathogen affecting cloven-hoof livestock. However, neither effective vaccines covering all serotypes nor specific antivirals against FMDV infections are currently available. In this study, we employed virtual screening to screen for secondary metabolite terpenoids targeting the RNA-dependent RNA polymerase (RdRp), or 3D pol , of FMDV. Subsequently, we identified the potential antiviral activity of the 32 top-ranked terpenoids, revealing that continentalic acid, dehydroabietic acid (abietic diterpenoids), brusatol, bruceine D, and bruceine E (tetracyclic triterpenoids) significantly reduced cytopathic effects and viral infection in the terpenoid-treated, FMDV-infected BHK-21 cells in a dose-dependent manner, with nanomolar to low micromolar levels. The FMDV minigenome assay demonstrated that brusatol and bruceine D, in particular, effectively blocked FMDV 3D pol activity, exhibiting IC50 values in the range of 0.37-0.39 µM and surpassing the efficacy of the antiviral drug control, ribavirin. Continentalic acid and bruceine E exhibited moderate inhibition of FMDV 3D pol . The predicted protein-ligand interaction confirmed that these potential terpenoids interacted with the main catalytic and bystander residues of FMDV 3D pol . Additionally, brusatol and bruceine D exhibited additive effects when combined with ribavirin. In conclusion, terpenoids from natural resources show promise for the development of anti-FMD agents.
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معلومات مُعتمدة: N42A670624 National Research Council of Thailand; 6705031590 Agricultural Research and Development Agency
فهرسة مساهمة: Keywords: FMDV 3Dpol; antiviral activity; foot-and-mouth disease virus (FMDV); terpenoids
المشرفين على المادة: 0 (Antiviral Agents)
0 (Terpenes)
EC 2.7.7.48 (RNA-Dependent RNA Polymerase)
0 (Diterpenes)
تواريخ الأحداث: Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11281344
DOI: 10.3390/v16071128
PMID: 39066290
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v16071128