Scale-up synthesis and antiviral mechanisms of novel fluorine-containing cytidine peptide compound SN15: Insights from transcriptomic and proteomic analyses
Miao Yu , Chuantao Xu , Yan Wang , Shidong Zhou , Jingwen Li , Zihao Xia , Mengnan An , He Liu , Yuanhua Wu
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引用次数: 0
Abstract
Cytidine peptide compounds have emerged as promising candidates for antiviral agents, but their large-scale production and mode of action remain underexplored. By optimizing temperature control and stirring efficiency, and replacing trifluoroacetic acid with an HCl/dioxane system for tert-butyloxycarbonyl (Boc) deprotection, efficient preparation of SN15 was achieved with a 78.47 % yield without the need for column chromatographic purification. Antiviral assays showed that SN15 inhibited TMV accumulation in single cells by 53.44 % at 250 μg/mL and significantly suppressed systemic infections by PVY, PMMoV, and TuMV, reducing viral RNA accumulation by 54.16 %, 41.14 %, and 61.85 %, respectively. Transcriptomic analysis identified 9676 differentially expressed genes (DEGs), with ribosomal protein-related pathways significantly upregulated and hormone signaling/ubiquitination pathways downregulated. Proteomic analysis revealed 216 differentially expressed proteins (DEPs), including ribosomal components and stress-response proteins, consistent with transcriptomic trends. Results of TRV-VIGS showed that silencing of 60S ribosomal protein L6 or lipid transfer-like protein VAS significantly increased TMV accumulation, confirming its critical role in antiviral defense, while silencing of peroxidase N1 precursor and E3 ubiquitin-protein ligase CIP8-like isoform X1 inhibited viral replication. This study reveals the molecular mechanism by which SN15 exerts antiviral effects through multi-pathway synergistic regulation, and provides a theoretical basis for the industrial production and broad-spectrum antiviral application of the fluorinated cytidine peptide compound SN15.
期刊介绍:
Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance.
Research Areas Emphasized Include the Biochemistry and Physiology of:
• Comparative toxicity
• Mode of action
• Pathophysiology
• Plant growth regulators
• Resistance
• Other effects of pesticides on both parasites and hosts.