The viral protein genome-linked protein (VPg) of telosma mosaic virus (TeMV) plays an important role in viral reproduction. In this study, the expression conditions of TeMV VPg were explored. A series of novel benzenesulfonamide derivatives were synthesized. The binding sites of the target compounds and TeMV VPg were studied by molecular docking, and the interaction was verified by microscale thermophoresis. The study revealed that the optimal expression conditions for TeMV VPg were in Escherichia coli Rosetta with IPTG concentration of 0.8 mM and induction temperature of 25 °C. Compounds A4, A6, A9, A16, and A17 exhibited excellent binding affinity to TeMV VPg, with K_d values of 0.23, 0.034, 0.19, 0.086, and 0.22 μM, respectively. LYS 121 is the key amino acid site. Compounds A9 inhibited the expression of TeMV VPg in Nicotiana benthamiana. The results suggested that TeMV VPg is a potential antiviral target to screen anti-TeMV compounds.

2023-07-01·Pest Management Science

Novel cinnamic acid derivatives as a versatile tool for developing agrochemicals for controlling plant virus and bacterial diseases by enhancing plant defense responses

Article

作者: Yang, Song ; Yang, Jie ; Liu, Li-Wei ; Wu, Zhi-Bing ; Zhou, Xiang ; Liu, Shuai-Shuai ; Liu, Hong-Wu ; Wang, Pei-Yi ; Yang, Bin-Xin ; Li, Zhen-Xing

AbstractBACKGROUNDPlant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity.RESULTSThe bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A5 (median effective concentration [EC50] = 287.7 μg mL−1), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC50 = 622.0 μg mL−1). In addition, compound A17 had a protective efficiency of 84.3% at 200 μg mL−1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion.CONCLUSIONThis research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry.

2023-06-18·Natural Product Research

Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum

Article

作者: Madeddu, Silvia ; Serreli, Gabriele ; Sanna, Giuseppina ; Manzin, Aldo ; Franke, Katrin ; Brandt, Wolfgang ; Fobofou, Serge A. T. ; Wessjohann, Ludger A.

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8' linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC₅₀ = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC₅₀ = 6.6-12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFV^R, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead.

100 项与 Angstrom-17 相关的药物交易

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