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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2025 · IF 6.2

Discovery of Arbutin as Novel Potential Antiviral Agent Against Tomato Yellow Leaf Curl Virus

Ying Xu,Tingting Zhang,Shimei Mu,Yanqun Peng,Duanpu Wu,Li Yang,Qing Li,Zengxue Wu,Jian Zhang

Tomato yellow leaf curl virus (TYLCV), a major plant virus, infects multiple plant species, severely threatening global food security. Arbutin, a natural product used in cosmetics to reduce pigmentation, also exhibits antibacterial and anti-inflammatory properties. However, its potential in plant protection remains undocumented. This study reveals arbutin’s ability to inhibit TYLCV infection. In Nicotiana benthamiana, 100 μg/mL arbutin inhibited viral gene accumulation by up to 76.8%, surpassing ningnanmycin (65.8%) and ribavirin (39.5%). Besides, microscale thermophoresis indicated that arbutin bound strongly to the TYLCV coat protein (CP). Molecular docking indicated that arbutin interacted with ARG58, VAL65, and CYS69. RT-qPCR and Western blot experiments confirmed the crucial roles of these amino acids, especially VAL65, in viral infection. Transcriptome analysis revealed that mutating VAL65 affected plant–pathogen interaction pathways and MAPK signaling in host defense mechanisms. This study unveils arbutin’s novel antiviral function, providing crucial insights for developing new biopesticides against plant viruses.

CAS / MDL: 497-76-7 36791-04-5
研究领域: 植物病理学 · 分子生物学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2025 · IF 3.1

A biomarker identified by integrated bronchoalveolar lavage fluid and lung tissue lipidomics mitigates respiratory syncytial virus infection

Shaodong Wang,Lili Lin,Yueyue Lei,Qiuyuan Li,Linxiu Peng

Respiratory syncytial virus (RSV) is a highly pathogenic respiratory virus that severely impacts infants under 2 years, adults over 60, and immunocompromised individuals. Currently, no safe, low-toxicity, or cost-effective therapy is available for RSV. Research indicates that RSV infection disrupts pulmonary surfactant lipid metabolism. Through lipidomic analysis of bronchoalveolar lavage (BAL) fluid and lung tissue, we observed an increase in most phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), while all phosphatidylglycerols (PGs) decreased. Additionally, all lysophospholipids in lung tissue increased. Among the altered lipids, 27 showed significant changes in both BAL fluid and lung tissue, including 15 phospholipids (7 PCs, 5 PEs, 3 PGs, and 1 phosphatidylinositol (PI)). From the decreased PGs, we identified an active lipid, PG 16:0–18:2, which correlated strongly between BAL fluid and lung tissue. Further studies confirmed that PG 16:0–18:2 significantly reduces viral load, mitigates RSV-induced lung damage, and reduces pulmonary inflammation. In vitro experiments demonstrated that PG 16:0–18:2 directly inhibits RSV replication and proliferation in epithelial cells. These findings suggest that PG 16:0–18:2 could serve as an effective and non-toxic antiviral agent, offering a promising complementary approach to RSV treatment.

CAS / MDL: 57-03-4
研究领域: 医学 · 生物学 · 病毒学 · 脂质代谢
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AQUACULTURE · 2021 · IF 4.242

Luteolin in Lonicera japonica inhibits the proliferation of white spot syndrome virus in the crayfish Procambarus clarkii

Hai-Feng Jiang,Cheng Chen,Xin-Yuan Jiang,Jing-Lei Shen,Fei Ling,Peng-Fei Li,Gao-Xue Wang

White spot disease caused by the white spot syndrome virus (WSSV) is a highly lethal infectious disease of crustacean aquaculture, with no effective means of control. Active compounds from herbal medicines are promising candidates for the development of antiviral agents for WSSV. We evaluated the efficacy of 12 herbal medicines in inhibiting WSSV proliferation in a WSSV infection model ( Procambarus clarkii ), Lonicera japonica extract had the strongest inhibitory effect on WSSV replication. Luteolin (LUT), the major bioactive compound of L. japonica extract, was further investigated and revealed to have a strong inhibitory effect on WSSV (96.04%, 50 mg/kg). LUT treatment decreased the WSSV load and the expression of important viral genes (immediate-early gene ie1 , DNA polymerase DNApol and envelope protein Vp28 ) in a dose-dependent manner and increased the survival of WSSV-infected crayfish by 60.00% (50 mg/kg). Co-incubation and time-of-addition assays revealed that LUT did not affect the infectivity of viral particles or viral absorption and entry. Expression of immune-related genes such as barrier-to-autointegration ( BAF ), heat shock protein 70 ( Hsp70 ) and signal transducer and activator of transcription ( STAT ), which may be beneficial for viral replication, were significantly decreased ( P  < 0.01) in LUT-treated crayfish. LUT also modified the expression of antioxidants ( SOD , CAT and GST ), pro-inflammatory factor ( COX-1 and COX-2 ), and apoptosis-related ( BAX and BI-1 ) genes ( P  < 0.01) to enhance antioxidant defenses, mitigate inflammation and induce apoptosis, respectively. Overall, LUT could be used as a prophylactic or therapeutic agent against WSSV infection in crustacean aquaculture.

CAS / MDL: 61-90-5 127-40-2
研究领域: 水产养殖 · 病毒学 · 药理学 · 免疫学
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STAR Protocols · 2022 · IF 0

Protocol for high-throughput screening of SARS-CoV-2 main protease inhibitors using a robust fluorescence polarization assay

Jing Zhang,Haohao Yan,Gangan Yan,Xiaoping Liu,Yanchang Wang,Yunyu Chen

Summary Discovery of efficacious antiviral agents targeting SARS-CoV-2 main protease (Mpro) is of the highest importance to fight against COVID-19. Here, we describe a simple protocol for high-throughput screening of Mpro inhibitors using a robust fluorescence polarization (FP) assay. Candidate Mpro inhibitors from large compound libraries could be rapidly identified by monitoring the change of millipolarization unit value. This affordable FP assay can be modified to screen antiviral agents targeting virus protease. For complete details on the use and execution of this protocol, please refer to Li et al. (2022) , Yan et al. (2021) , and Yan et al. (2022c) .

研究领域: 病毒学 · 药学 · 分子生物学
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PEST MANAGEMENT SCIENCE · 2024 · IF 3.8

Design, synthesis and Anti-PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane

Liangzhen Shu,Ya Lv,Zhongyin Chen,Yixian Huang,Meng Zhang,Zhichao Jin,Tingting Li,Yonggui Robin Chi

BACKGROUND Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N -heterocyclic carbene-catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY. RESULTS The absolute configurations of the planar chiral compounds exhibited obvious distinctions in the anti-PVY activities. Notability, compound ( S )- 4u exhibited remarkable curative activities against PVY, with a half maximal effective concentration (EC 50 ) of 349.3 μg mL −1 , which was lower than that of the ningnanmycin (NNM) (EC 50 = 400.8 μg mL −1 ). Additionally, The EC 50 value for the protective effects of ( S )- 4u was 146.2 μg mL −1 , which was superior to that of NNM (276.4 μg mL −1 ). Furthermore, the mechanism-of-action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests. CONCLUSION Biological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY-CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities. © 2024 Society of Chemical Industry.

研究领域: 植物病理学 · 有机化学 · 药学 · 生物化学 · 农业科学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Discovery of Novel Chiral Indole Derivatives Containing the Oxazoline Moiety as Potential Antiviral Agents for Plants

Yixian Huang,Xiaolin Peng,Jinli Chen,Liangzhen Shu,Meng Zhang,Jiamiao Jin,Zhichao Jin,Yonggui Robin Chi

Potato virus Y (PVY) is an important plant virus that has spread worldwide, causing significant economic losses. To search for novel structures as potent antiviral agents, a series of chiral indole derivatives containing oxazoline moieties were designed and synthesized and their anti-PVY activities were evaluated. Biological activity tests demonstrated that many chiral compounds exhibited promising anti-PVY activities and that their absolute configurations exhibited obvious distinctions in antiviral bioactivities. Notably, compound (S)-4v displayed excellent curative and protective efficacy against PVY, with EC50 values of 328.6 and 256.1 μg/mL, respectively, which were superior to those of commercial virucide ningnanmycin (NNM, 437.4 and 397.4 μg/mL, respectively). The preliminary antiviral mechanism was investigated to determine the difference in antiviral activity between the two enantiomers of 4v chiral compounds. Molecular docking indicated a stronger binding affinity between the coating proteins of PVY (PVY-CP) and (S)-4v (−6.5 kcal/mol) compared to (R)-4v (−6.2 kcal/mol). Additionally, compound (S)-4v can increase the chlorophyll content and defense-related enzyme activities more effectively than its enantiomer. Therefore, this study provides an important basis for the development of chiral indole derivatives containing oxazoline moieties as novel agricultural chemicals.

研究领域: 植物病理学 · 药物化学 · 农业科学
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Nature Catalysis · 2022 ·Vol. 5 ·期 8 ·694-707 · IF 40.706

Site-selective proteolytic cleavage of plant viruses by photoactive chiral nanoparticles

Gao Rui,Xu Liguang,Sun Maozhong,Xu Manlin,Hao Changlong,Guo Xiao,Colombari Felippe Mariano,Zheng Xin,Král Petr,de Moura André F.,Xu Chuanlai,Yang Jinguang,Kotov Nicholas A.,Kuang Hua

Viral diseases of plants are associated with large health and economic costs. Antiviral agents developed for mammalian organisms have had limited success for plants, necessitating alternative strategies to address this biological and sustainability problem. Here we show that chiral 3 nm Cu 1.96 S nanoparticles can site-selectively cleave capsid in tobacco mosaic virus under sunlight. With d - penicillamine as surface ligands, the nanoparticles display high affinity to the Gln 99 to Ala 105 segment in the capsid via a network of supramolecular bonds and 3,000–10,000 times lower affinity to capsids of other viruses. Illumination with green light leads to polarization-dependent, protease-like hydrolysis of the amide bond between Asn 101 and Pro 102. Nanoparticles inhibited viral infectivity by 98.7% in protoplasts and 92.6% in plants while avoiding hypersensitive response and large environmental impact. These findings show that nanoparticles combining proteolytic activity due to metal ions and site selectivity due to nanoscale chirality can be used as effective antiviral agents.

CAS / MDL: 7697-37-2
研究领域: 植物病毒学 · 纳米技术 · 生物技术
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Dufulin Intervenes the Viroplasmic Proteins as the Mechanism of Action against Southern Rice Black-Streaked Dwarf Virus

Dongmei Wang,Xin Xie,Di Gao,Kai Chen,Zhuo Chen,Linhong Jin,Xiangyang Li,Baoan Song

Southern rice black-streaked dwarf virus (SRBSDV) causes disease in crops, which reduces the quality and yield. Several commercial antiviral agents are available to control the SRBSDV induced disease. However, the mechanism of antiviral agents controlling SRBSDV is largely unknown. Identifying targets in SRBSDV is a key step of antiviral agent discovery. Here, we investigated the potential protein target of the antiviral agent dufulin. We cloned and expressed a soluble viroplasmic P6 protein in the prokaryote Escherichia coli and the eukaryote Spodoptera frugiperda 9. The dissociation constants of dufulin with the purified P6 protein from E. coli and S. frugiperda 9 expression systems were 4.49 and 4.95 μM, respectively, indicating a strong binding affinity between dufulin and P6 protein. In vivo, dufulin significantly inhibited the expression of both P6 protein and P6 gene in the SRBSDV-infected rice leaves. This inhibition on P6 protein expression was also observed in transformed Nicotiana benthamiana where the P6 was overexpressed. Our data also showed that dufulin inhibited the duplication of SRBSDV in a dose-dependent manner in infected rice leaves with a half maximum effective concentration of 3.32 mM. It is therefore concluded that dufulin targets the viroplasmic protein P6 to inhibit the virulence of SRBSDV.

CAS / MDL: 1317-42-6
研究领域: 植物病理学 · 病毒学 · 农业科学
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