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Identification of Carbazole Alkaloid Derivatives with Acylhydrazone as Novel Anti-TMV Agents with the Guidance of a Digital Fluorescence Visual Screening

文献类型: 外文期刊

作者: Zhang, Xianpeng 1 ; Huang, Wenbo 3 ; Lu, Xu 4 ; Liu, Sisi 5 ; Feng, Hui 6 ; Yang, Wanneng 7 ; Ye, Junli 7 ; Li, Feng 4 ; Ke, 1 ;

作者机构: 1.Huazhong Agr Univ, Coll Vet Med, State Key Lab Agr Microbiol, Wuhan 430070, Hubei, Peoples R China

2.Huazhong Agr Univ, Coll Plant Sci & Technol, Wuhan 430070, Hubei, Peoples R China

3.Hubei Acad Agr Sci, Natl Biopesticide Engn Res Ctr, Hubei Biopesticide Engn Res Ctr, Wuhan 430064, Hubei, Peoples R China

4.Huazhong Agr Univ, Coll Hort & Forestry Sci, Key Lab Hort Biol, Minist Educ, Wuhan 430070, Hubei, Peoples R China

5.Huazhong Agr Univ, Coll Sci, Wuhan 430070, Hubei, Peoples R China

6.Huazhong Agr Univ, Coll Informat, Wuhan 430070, Hubei, Peoples R China

7.Huazhong Agr Univ, Natl Ctr Plant Gene Res, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China

8.Huazhong Agr Univ, Natl Reference Lab Vet Drug Residues HZAU, Wuhan 430070, Hubei, Peoples R China

9.Huazhong Agr Univ, MAO Key Lab Detect Vet Drug Residues, Wuhan 430070, Hubei, Peoples R China

关键词: digital and visual antiviral screening; tobacco mosaic virus; green fluorescence protein; carbazole alkaloids; beta-carboline alkaloids

期刊名称:JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ( 影响因子:5.279; 五年影响因子:5.269 )

ISSN: 0021-8561

年卷期: 2021 年 69 卷 26 期

页码:

收录情况: SCI

摘要: Difficulty in preventing crops from plant viruses urges to discover novel efficient antiviral chemicals, which is sped up by precise screening methods. Fluorescence-based methods have recently been applied as innovative and rapid tools for visually monitoring the replication of viruses and screening of antivirals, whereas the quantification of fluorescence signals mainly depends on manually calculating the fluorescent spots, which is time-consuming and imprecise. In the present work, the fluorescence spots were automatically identified, and the fluorescence area was directly quantified by a program developed in our group, which avoided subjective errors from the operators. We further employed this digital and visual screening assay to identify antivirals using the tobacco mosaic virus-green fluorescence protein (TMV-GFP) construct, in which the expression of GFP intuitively reflected the efficacy of antivirals. The accuracy of this assay was validated by quantifying the activities of the commercial antiviral inhibitors ribavirin and ningnanmycin and then was applied to evaluate the subtle activity differences of a series of newly synthesized carbazole and beta-carboline alkaloid derivatives. Among them, compounds 5 (76%) and 11 (63%) exhibited anti-TMV activities comparable to that of ningnanmycin (65%) at 50 mu M, and they delayed the multiplication of TMV in the early stage of infection without phytotoxicity. Taken together, these findings demonstrated that the digital and visual TMV-GFP screening method was competent to test the antiviral activities of compounds with subtle modifications and facilitated the discovery of novel antivirals.

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