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1.
Pestic Biochem Physiol ; 166: 104449, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32448412

RESUMO

Tobacco mosaic virus helicase (TMV-Hel) plays important roles in viral multiplication. TMV-Hel is a potential target of anti-TMV agents. Our previous studies expressed and purified TMV-Hel as target protein for cytosinpeptidemycin. In this study, we preform molecular docking to study the binding sites of commercial antiviral agents with TMV-Hel. Then we verify the interactions between the potential anti-TMV agents and TMV-Hel in vitro using Microscale Thermophoresis experiment and study the inhibiting expression of TMV-Hel with the potential anti-TMV agents in vivo using Western-blot (WB) method. The results showed that ribavirin bound to TMV-Hel with a dissociation constant of 1.55 µM by direct interaction with eight binding sites, which was consistent with the docking studies. Ribavirin inhibited the expression of TMV-Hel in Nicotiana benthamiana. Docking studies combined Microscale Thermophoresis and WB experiment provided a new method to screen anti-TMV agents targeting TMV-Hel.


Assuntos
Antivirais , Vírus do Mosaico do Tabaco , Simulação de Acoplamento Molecular , Tabaco
2.
Pestic Biochem Physiol ; 166: 104568, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32448422

RESUMO

Thirty unreported indole derivatives containing dithioacetal moiety were synthesized and evaluated for anti-plant viral activity. Bioassay results displayed that some of the target compounds showed better activities against tobacco mosaic virus (TMV) than the commercial Ribavirin in vivo. In particular, anti-TMV curative, protective and inactivating activity of 4p were 55.1, 57.2, and 80.3%, respectively, and EC50 value for inactivating activity was 88.5 µg/mL. The observation of transmission electron microscope showed that 4p may have a certain destructive effect on TMV particles. To further study, microscale thermophoresis analysis result also demonstrated that 4p powerfully interacted with TMV coat protein in vitro. Hence, this study provides a strong evidence suporting that indole derivatives might be applied as new antiviral agents.


Assuntos
Antivirais , Vírus do Mosaico do Tabaco , Indóis , Relação Estrutura-Atividade
3.
Pestic Biochem Physiol ; 164: 115-121, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284116

RESUMO

A series of cinnamic acid derivatives, which contained dithioacetal moiety, were designed and synthesized, and their anti-plant virus activity against Tobacco mosaic virus (TMV) were evaluated. Most target compounds exhibited good anti-plant virus activities. Compound 2y, especially at 500 mg/L concentration, had an excellent activity against TMV, and its curative, protective, and inactivating activities were 62.5%, 61.8%, and 83.5%, respectively. These activity values were significantly superior to those of ribavirin (45.9%, 39.8%, and 70.3%) and xiangcaoliusuobingmi (44.7%, 48.3%, and 71.7%) and comparable to those of ningnanmycin (61.9%, 53.3%, and 85.2%). Compound 2y presented an EC50 value of 50.7 mg/L for inactivating activity against TMV, which was superior to those of ningnanmycin (51.5 mg/L), ribavirin (160.4 mg/L), and xiangcaoliusuobingmi (83.0 mg/L). Through transmission electron microscopy, we found that compound 2y caused a certain degree of damage to TMV particles, which caused them to break and bend. Four conventional hydrogen bonds were formed with amino acid residues GLN34, THR37, ARG90, and ARG46 of TMV coat protein (CP) through molecular docking. Microscale thermophoresis test results showed that compound 2y with TMV CP had a strong binding force, and the dissociation constant (Kd) was 1.6 µM. In summary, the cinnamic acid derivatives containing dithioacetal moiety provide a foundation for further research on antiviral agents.


Assuntos
Antivirais , Vírus do Mosaico do Tabaco , Cinamatos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
4.
Pestic Biochem Physiol ; 164: 40-46, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284135

RESUMO

Plant viral diseases cause severe economic losses in agricultural production. Development of microorganism-derived antiviral agents provides an alternative strategy to efficiently control plant viral diseases. In this study, the antiviral effect and mechanism of a combined biological agent Cytosinpeptidemycin and Chitosan oligosaccharide (CytPM-COS) were investigated. CytPM-COS effectively inhibited tobacco mosaic virus (TMV) in Nicotiana glutinosa, suppressed viral RNA and CP accumulation in BY-2 protoplast and affected the subcellular localization as well as punctate formation of TMV MP in N. benthamiana leaves. In addition, CytPM-COS triggered reactive oxygen species (ROS) production and induced up-regulation of various defense responsive genes including PR-1, PR-5, FLS2, Hsp70. Our results indicated that CytPM-COS can potentially act as a pesticide for integrated control of plant viruses in the future.


Assuntos
Antivirais , Quitosana , Vírus do Mosaico do Tabaco , Fatores Biológicos , Citosina/análogos & derivados , Oligossacarídeos , Doenças das Plantas , Folhas de Planta , Tabaco
5.
PLoS One ; 15(3): e0224534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231371

RESUMO

Virus resistance genes carried by wild plant species are valuable resources for plant breeding. The Rysto gene, conferring a broad spectrum of durable resistance, originated from Solanum stoloniferum and was introgressed into several commercial potato cultivars, including 'White Lady', by classical breeding. Rysto was mapped to chromosome XII in potato, and markers used for marker-assisted selection in breeding programmes were identified. Nevertheless, there was no information on the identity of the Rysto gene. To begin to reveal the identification of Rysto, fine-scale genetic mapping was performed which, in combination with chromosome walking, narrowed down the locus of the gene to approximately 1 Mb. DNA sequence analysis of the locus identified six full-length NBS-LRR-type (short NLR-type) putative resistance genes. Two of them, designated TMV2 and TMV3, were similar to a TMV resistance gene isolated from tobacco and to Y-1, which co-segregates with Ryadg, the extreme virus resistance gene originated from Solanum andigena and localised to chromosome XI. Furthermore, TMV2 of 'White Lady' was found to be 95% identical at the genomic sequence level with the recently isolated Rysto gene of the potato cultivar 'Alicja'. In addition to the markers identified earlier, this work generated five tightly linked new markers which can serve potato breeding efforts for extreme virus resistance.


Assuntos
Mapeamento Cromossômico , Cromossomos de Plantas/genética , Resistência à Doença/genética , Doenças das Plantas/genética , Solanum tuberosum/genética , Vírus do Mosaico do Tabaco , Doenças das Plantas/virologia , Solanum tuberosum/virologia
6.
Acta Crystallogr D Struct Biol ; 76(Pt 4): 332-339, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32254057

RESUMO

Confidence maps provide complementary information for interpreting cryo-EM densities as they indicate statistical significance with respect to background noise. They can be thresholded by specifying the expected false-discovery rate (FDR), and the displayed volume shows the parts of the map that have the corresponding level of significance. Here, the basic statistical concepts of confidence maps are reviewed and practical guidance is provided for their interpretation and usage inside the CCP-EM suite. Limitations of the approach are discussed and extensions towards other error criteria such as the family-wise error rate are presented. The observed map features can be rendered at a common isosurface threshold, which is particularly beneficial for the interpretation of weak and noisy densities. In the current article, a practical guide is provided to the recommended usage of confidence maps.


Assuntos
Microscopia Crioeletrônica/métodos , ATPases Bacterianas Próton-Translocadoras/química , Gráficos por Computador , Modelos Moleculares , Conformação Proteica , Ribossomos/química , Eletricidade Estática , Estatística como Assunto , Vírus do Mosaico do Tabaco , Interface Usuário-Computador
7.
Phytopathology ; 110(6): 1189-1198, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32141384

RESUMO

The harpin protein Hpa1 has various beneficial effects in plants, such as promoting plant growth and inducing pathogen resistance. Our previous study found that Hpa1 could significantly alleviate the mosaic symptoms of tobacco mosaic virus (TMV) in Pinellia ternata, indicating that Hpa1 can effectively stimulate resistance. Here, the potential mechanism of disease resistance and field applicability of Hpa1 against TMV in P. ternata were further investigated. The results showed that 15 µg ml-1 Hpa1 had stronger antiviral activity than the control, and its protective effect was better than its curative effect. Furthermore, Hpa1 could significantly induce an increase in defense-related enzyme activity, including polyphenol oxidase, peroxidase, catalase, and superoxide dismutase, as well as increase the expression of disease resistance-related genes (PR1, PR3, PR5, and PDF1.2). Concurrently, Hpa1 significantly increased the content of some disease resistance-related substances, including hydrogen peroxide, phenolics, and callose, whereas the content of malondialdehyde was reduced. In addition, field application analysis demonstrated that Hpa1 could effectively elicit a defense response against TMV in P. ternata. Our findings propose a mechanism by which Hpa1 can prevent TMV infection in Pinellia by inducing systemic resistance, thereby providing an environmentally friendly approach for the use of Hpa1 in large-scale applications to improve TMV resistance in Pinellia.


Assuntos
Pinellia , Vírus do Mosaico do Tabaco , Resistência à Doença , Humanos , Doenças das Plantas , Tabaco
8.
Biochemistry (Mosc) ; 85(2): 224-233, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32093598

RESUMO

Recently we obtained complexes between genetically modified Tobacco Mosaic Virus (TMV) particles and proteins carrying conserved influenza antigen such as M2e epitope. Viral vector TMV-N-lys based on TMV-U1 genome was constructed by insertion of chemically active lysine into the exposed N-terminal part of the coat protein. Nicotiana benthamiana plants were agroinjected and TMV-N-lys virions were purified from non-inoculated leaves. Preparation was analyzed by SDS-PAGE/Coomassie staining; main protein with electrophoretic mobility of 21 kDa was detected. Electron microscopy confirmed the stability of modified particles. Chemical conjugation of TMV-N-lys virions and target influenza antigen M2e expressed in E. coli was performed using 5 mM 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and 1 mM N-hydroxysuccinimide. The efficiency of chemical conjugation was confirmed by Western blotting. For additional characterization we used conventional electron microscopy. The diameter of the complexes did not differ significantly from the initial TMV-N-lys virions, but complexes formed highly organized and extensive network with dense "grains" on the surface. Dynamic light scattering demonstrated that the single peaks, reflecting the complexes TMV-N-lys/DHFR-M2e were significantly shifted relative to the control TMV-N-lys virions. The indirect enzyme-linked immunosorbent assay with TMV- and DHFR-M2e-specific antibodies showed that the complexes retain stability during overnight adsorption. Thus, the results allow using these complexes for immunization of animals with the subsequent preparation of a candidate universal vaccine against the influenza virus.


Assuntos
Antígenos Virais/química , Vírus do Mosaico do Tabaco/química , Proteínas da Matriz Viral/química , Agrobacterium tumefaciens/citologia , Agrobacterium tumefaciens/virologia , Antígenos Virais/imunologia , Humanos , Influenza Humana/imunologia , Vírus do Mosaico do Tabaco/genética , Vírus do Mosaico do Tabaco/imunologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia
9.
J Agric Food Chem ; 68(9): 2631-2638, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32023057

RESUMO

Previously, we reported for the first time that harmala alkaloids harmine and tetrahydroharmine exhibit activity against plant viruses, and we developed an analogue, designated NK0209, that efficiently prevents and controls plant virus diseases. Here, to investigate the influence of the spatial configuration of NK0209 on its antiviral activities, we synthesized its four optical isomers, determined their configurations, and evaluated their activities against tobacco mosaic virus. All four isomers were significantly more active than ningnanmycin, which is one of the most successful commercial antiviral agents, with in vivo inactivation, cure, and protection rates of 57.3 ± 1.9, 54.2 ± 3.3, and 55.0 ± 4.1% at 500 µg/mL. Furthermore, analysis of structure-activity relationships demonstrated for the first time that the spatial conformation of NK0209 is an important determinant of its antiviral activity, and our results provide information about the possible optimum configuration for interaction of this molecule with its target protein.


Assuntos
Antivirais/química , Antivirais/farmacologia , Harmina/química , Harmina/farmacologia , Vírus de Plantas/efeitos dos fármacos , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Antivirais/síntese química , Desenho de Fármacos , Harmina/síntese química , Isomerismo , Conformação Molecular , Doenças das Plantas/virologia , Vírus de Plantas/crescimento & desenvolvimento , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/crescimento & desenvolvimento
10.
Org Biomol Chem ; 18(10): 1881-1885, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32100807

RESUMO

A convenient two-step method is reported for the ligation of alkoxyamine- or hydrazine-bearing cargo to proline N-termini. Using this approach, bifunctional proline N-terminal bioconjugates are constructed and proline N-terminal proteins are immobilized.


Assuntos
Aminas/química , Hidrazinas/química , Prolina/química , Proteínas/síntese química , Hidrazonas/síntese química , Cetonas/síntese química , Oxirredução , Oximas/síntese química , Pyrococcus furiosus/química , Vírus do Mosaico do Tabaco/química
11.
J Agric Food Chem ; 68(4): 975-981, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31891504

RESUMO

In this study, a series of coumarin derivatives containing dithioacetals were synthesized, characterized, and assessed for their anti-tobacco mosaic virus (TMV) activities. Biological tests showed that most of the title compounds exhibited significant anti-TMV biological activities; in particular, compound b21 showed good inactivating activity anti-TMV, with an EC50 of 54.2 mg/L, superior to that of ribavirin (134.2 mg/L). Transmission electron microscopy analyses showed that compound 21 severely ruptured TMV particles. The interaction of compound b21 with TMV coat protein (TMV CP) was investigated using microscale thermophoresis and molecular docking. Compound b21 exhibited a strong binding ability to TMV CP, with a value of 2.9 µM, superior to ribavirin.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Antivirais/química , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Cumarínicos/química , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/fisiologia
12.
Proc Natl Acad Sci U S A ; 117(6): 3114-3122, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31988134

RESUMO

Plasmodium falciparum vaccine RTS,S/AS01 is based on the major NPNA repeat and the C-terminal region of the circumsporozoite protein (CSP). RTS,S-induced NPNA-specific antibody titer and avidity have been associated with high-level protection in naïve subjects, but efficacy and longevity in target populations is relatively low. In an effort to improve upon RTS,S, a minimal repeat-only, epitope-focused, protective, malaria vaccine was designed. Repeat antigen copy number and flexibility was optimized using the tobacco mosaic virus (TMV) display platform. Comparing antigenicity of TMV displaying 3 to 20 copies of NPNA revealed that low copy number can reduce the abundance of low-affinity monoclonal antibody (mAb) epitopes while retaining high-affinity mAb epitopes. TMV presentation improved titer and avidity of repeat-specific Abs compared to a nearly full-length protein vaccine (FL-CSP). NPNAx5 antigen displayed as a loop on the TMV particle was found to be most optimal and its efficacy could be further augmented by combination with a human-use adjuvant ALFQ that contains immune-stimulators. These data were confirmed in rhesus macaques where a low dose of TMV-NPNAx5 elicited Abs that persisted at functional levels for up to 11 mo. We show here a complex association between NPNA copy number, flexibility, antigenicity, immunogenicity, and efficacy of CSP-based vaccines. We hypothesize that designing minimal epitope CSP vaccines could confer better and more durable protection against malaria. Preclinical data presented here supports the evaluation of TMV-NPNAx5/ALFQ in human trials.


Assuntos
Anticorpos Antiprotozoários/imunologia , Vacinas Antimaláricas , Malária Falciparum/imunologia , Plasmodium falciparum , Proteínas de Protozoários , Vírus do Mosaico do Tabaco/genética , Animais , Células HEK293 , Humanos , Imunogenicidade da Vacina , Macaca mulatta , Vacinas Antimaláricas/química , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Engenharia de Proteínas , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia
13.
Phytopathology ; 110(1): 194-205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31502520

RESUMO

Tobacco mosaic virus (TMV) is an extensively studied RNA virus known to infect tobacco (Nicotiana tabacum) and other solanaceous crops. TMV has been classified as a seedborne virus in tobacco, with infection of developing seedlings thought to occur from contact with the TMV-infected seed coat. The mechanism of TMV transmission through seed was studied in seed of the K 326 cultivar of flue-cured tobacco. Cross pollinations were performed to determine the effect of parental tissue on TMV infection in seed. Dissection of individual tobacco seeds into seed coat, endosperm, and embryo was performed to determine TMV location within a seed, while germination tests and separation of the developing seedling into seed coat, roots, and cotyledons were conducted to estimate the percent transmission of TMV. A reverse-transcriptase quantitative PCR (RT-qPCR) assay was developed and used to determine TMV concentrations in individual seed harvested from pods that formed on plants from TMV-infected and noninfected crosses. The results showed maternal transmission of TMV to tobacco seed and seedlings that developed from infected seed, not paternal transmission. RT-qPCR and endpoint PCR assays were also conducted on the separated seed coat, endosperm, and embryo of individual seed and separated cotyledons, roots, and seed coats of individual seedlings that developed from infected tobacco seed to identify the location of the virus in the seed and the subsequent path the virus takes to infect the developing seedling. RT-qPCR and endpoint PCR assay results showed evidence of TMV infection in the endosperm and embryo, as well as in the developing seedling roots and cotyledons within 10 days of initiating seed germination. To our knowledge, this is the first report of TMV being detected in embryos of tobacco seed, demonstrating that TMV is seedborne and seed-transmitted in flue-cured tobacco.


Assuntos
Reação em Cadeia da Polimerase em Tempo Real , Vírus do Mosaico do Tabaco , Tabaco , Doenças das Plantas/virologia , Plântula/virologia , Sementes/virologia , Tabaco/virologia , Vírus do Mosaico do Tabaco/genética , Vírus do Mosaico do Tabaco/fisiologia
14.
J Agric Food Chem ; 68(2): 471-484, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31841334

RESUMO

Plant diseases seriously affect crop yield and quality and are difficult to control. Marine natural products (MNPs) have become an important source of drug candidates with new biological mechanisms. Marine natural product essramycin (1) was found to have good anti-tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities for the first time. A series of essramycin derivatives were designed, synthesized, and evaluated for their bioactivity. Most of these compounds exhibited antiviral effects that are greater than that of the control ribavirin. Compounds 7e and 8f displayed antiviral activities that are greater than that of ningnanmycin (the most widely used antiviral agent at present), thus emerging as novel antiviral lead compounds. As the lead compound, 7e was selected for further antiviral mechanism research. The results indicated that 7e could inhibit virus assembly and promote 20S disk protein aggregation. Fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that essramycin analogues displayed broad-spectrum fungicidal activities. Compound 5b displayed more than 50% inhibition rate against most of the 14 kinds of phytopathogenic fungi at 50 µg/mL. The current research lays a solid foundation for the application of essramycin alkaloids in crop protection.


Assuntos
Alcaloides/química , Antivirais/química , Fungicidas Industriais/química , Pirimidinonas/química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Triazóis/química , Alcaloides/farmacologia , Antivirais/farmacologia , Fungos/efeitos dos fármacos , Fungos/fisiologia , Fungicidas Industriais/farmacologia , Estrutura Molecular , Doenças das Plantas/microbiologia , Pirimidinonas/farmacologia , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/fisiologia , Triazóis/farmacologia , Montagem de Vírus/efeitos dos fármacos
15.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878172

RESUMO

The coumarin compound of osthole was extracted from Cnidium monnieri and identified by LC-MS and 1H- and 13C-NMR. Osthole was tested for anti-virus activity against tobacco mosaic virus (TMV) using the half-leaf method. The results showed that stronger antiviral activity on TMV infection appeared in Nicotiana glutinosa than that of eugenol and ningnanmycin, with inhibitory, protective, and curative effects of 72.57%, 70.26%, and 61.97%, respectively. Through observation of the TMV particles, we found that osthole could directly affect the viral particles. Correspondingly, the level of coat protein detected by Western blot was significantly reduced when the concentrations of osthole increased in tested plants compared to that of the control. These results suggest that osthole has anti-TMV activity and may be used as a biological reagent to control the plant virus in the half-leaf method.


Assuntos
Cnidium/química , Cumarínicos/farmacologia , Doenças das Plantas/terapia , Doenças das Plantas/virologia , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/fisiologia , Tabaco/virologia , Antivirais/farmacologia , Proteínas do Capsídeo/metabolismo , Cumarínicos/química , Cinética , Vírus do Mosaico do Tabaco/ultraestrutura , Vírion/efeitos dos fármacos , Vírion/ultraestrutura
16.
J Agric Food Chem ; 67(48): 13344-13352, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31721573

RESUMO

A series of novel anthranilic diamide derivatives (5a-5ab) containing moieties of trifluoromethylpyridine and hydrazone was designed and synthesized. The synthesized compounds were evaluated in vivo for their activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Most of the synthesized compounds displayed good to excellent antiviral activities. The compounds 5i, 5k, 5s, 5w, 5x, and 5z had the curative activity over 65% against TMV at the concentration of 500 µg/mL, which were significantly higher than those of ningnanmycin (55.0%) and ribavirin (37.9%). Notably, the curative activity of compound 5i was up to 79.5%, with the EC50 value of 75.9 µg/mL, whereas the EC50 value of ningnanmycin was 362.4 µg/mL. The pot experiments also further demonstrated the significantly curative effect of 5i. Meanwhile, compounds 5h, 5p and 5x displayed more protective activities on TMV than that of ningnanmycin. Moreover, compounds 5a, 5e, 5f, and 5i showed inactivation activity similar to ningnanmycin at 500 µg/mL, and the EC50 value of 5e (41.5 µg/mL) was lower than ningnanmycin (50.0 µg/mL). The findings of transmission electron microscopic (TEM) indicated that the synthesized compounds exhibited strong and significant binding affinity to TMV coat protein (CP) and could obstruct the self-assembly and increment of TMV particles. Microscale thermophoresis (MST) studies on TMV-CP and CMV CP revealed that some of the active compounds, particularly 5i, exhibited a strong binding capability to TMV-CP or CMV-CP. This study revealed that anthranilic diamide derivatives containing moieties of trifluoromethylpyridine and hydrazone could be used as novel antiviral agents for controlling the plant viruses.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Diamida/química , Hidrazonas/química , Vírus de Plantas/efeitos dos fármacos , Piridinas/química , Antivirais/química , Cucumovirus/efeitos dos fármacos , Cucumovirus/crescimento & desenvolvimento , Diamida/farmacologia , Desenho de Fármacos , Hidrazonas/farmacologia , Testes de Sensibilidade Microbiana , Vírus de Plantas/crescimento & desenvolvimento , Piridinas/síntese química , Piridinas/farmacologia , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/crescimento & desenvolvimento
17.
J Agric Food Chem ; 67(50): 13882-13891, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31721582

RESUMO

A series of compounds with potential activity to induce plant resistance was synthesized from indole and thiol compounds and methodically evaluated for antiviral activity. The results indicated that some of the synthesized compounds had high antipotato virus Y (PVY), anticucumber mosaic virus, and antitobacco mosaic virus activities. Notably, compound D21 exhibited the best activity against PVY among these compounds in vivo, and the 50% effective concentrations (EC50) of protection activity is 122 µg/mL, which was distinctively better than the corresponding values for ribavirin (653 µg/mL), Ningnanmycin (464 µg/mL), and Xiangcaoliusuobingmi (279 µg/mL). Interestingly, we found that the protection activity of D21 was associated with improvement of chlorophyll content and defense-related enzyme activities. Moreover, D21 could trigger the malate dehydrogenase (MDH) signaling pathway, as further confirmed by the MDH activity evaluation. Hence, D21 can protect plants against viral activity and has potential as a novel activator for plant resistance induction.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Indóis/farmacologia , Doenças das Plantas/virologia , Antivirais/química , Desenho de Fármacos , Indóis/química , Potyvirus/efeitos dos fármacos , Potyvirus/crescimento & desenvolvimento , Relação Estrutura-Atividade , Tabaco/virologia , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/crescimento & desenvolvimento
18.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717281

RESUMO

Huanglongbing (HLB), also known as citrus greening, is the most destructive disease of citrus worldwide. HLB is associated with the non-culturable bacterium, Candidatus Liberibacter asiaticus (CaLas) in the United States. The virulence mechanism of CaLas is largely unknown, partly because of the lack of a mutant library. In this study, Tobacco mosaic virus (TMV) and Nicotiana benthamiana (N. benthamiana) were used for large-scale screening of the virulence factors of CaLas. Agroinfiltration of 60 putative virulence factors in N. benthamiana led to the identification of four candidates that caused severe symptoms in N. benthamiana, such as growth inhibition and cell death. CLIBASIA_05150 and CLIBASIA_04065C (C-terminal of CLIBASIA_04065) could cause cell death in the infiltrated leaves at five days post infiltration. Two low-molecular-weight candidates, CLIBASIA_00470 and CLIBASIA_04025, could inhibit plant growth. By converting start codon to stop codon or frameshifting, the four genes lost their harmful effects to N. benthamiana. It indicated that the four virulence factors functioned at the protein level rather than at the RNA level. The subcellular localization of the four candidates was determined by confocal laser scanning microscope. CLIBASIA_05150 located in the Golgi apparatus; CLIBASIA_04065 located in the mitochondrion; CLIBASIA_00470 and CLIBASIA_04025 distributed in cells as free GFP. The host proteins interacting with the four virulence factors were identified by yeast two-hybrid. The host proteins interacting with CLIBASIA_00470 and CLIBASIA_04025 were overlapping. Based on the phenotypes, the subcellular localization and the host proteins identified by yeast two-hybrid, CLIBASIA_00470 and CLIBASIA_04025, functioned redundantly. The hypothesis of CaLas virulence was proposed. CaLas affects citrus development and suppresses citrus disease resistance, comprehensively, in a complicated manner. Ubiquitin-mediated protein degradation might play a vital role in CaLas virulence. Deep characterization of the interactions between the identified virulence factors and their prey will shed light on HLB. Eventually, it will help in developing HLB-resistant citrus and save the endangered citrus industry worldwide.


Assuntos
Rhizobiaceae/patogenicidade , Vírus do Mosaico do Tabaco/metabolismo , Tabaco/metabolismo , Tabaco/microbiologia , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Morte Celular , Fenótipo , Folhas de Planta/citologia , Folhas de Planta/microbiologia , Frações Subcelulares/metabolismo , Tabaco/virologia
19.
Proc Natl Acad Sci U S A ; 116(47): 23437-23443, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685638

RESUMO

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.


Assuntos
Ácidos Acíclicos/farmacologia , Antibacterianos/farmacologia , Proteínas do Capsídeo/farmacologia , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Produtos do Gene tat/farmacologia , Compostos Organoplatínicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Estilbenos/farmacologia , Ácidos Acíclicos/química , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/efeitos da radiação , Escherichia coli/ultraestrutura , Microscopia Eletrônica , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Staphylococcus aureus/efeitos da radiação , Staphylococcus aureus/ultraestrutura , Eletricidade Estática , Vírus do Mosaico do Tabaco
20.
Molecules ; 24(20)2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635044

RESUMO

As a continuation of our efforts to discover and develop "me-better" active molecules, in this study, a series of novel isoxazole-amide derivatives containing an acylhydrazone moiety were synthesized and evaluated for their antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Antiviral bioassays indicated that some of the target compounds exhibited better in vivo antiviral activities against TMV and CMV than those of Ningnanmycin (NNM). Especially, the compound 7t exhibited the best curative, protection, and inactivation activities against TMV and CMV which were superior to those of NNM. Meanwhile, our present work also revealed that compound 7t could enhance the defense-related enzyme activity and increase the chlorophyll content in tobacco leaves to induce resistance and enhance plant tolerance to TMV infection.


Assuntos
Antivirais/síntese química , Hidrazonas/química , Isoxazóis/síntese química , Antivirais/química , Antivirais/farmacologia , Clorofila/metabolismo , Cucumovirus/efeitos dos fármacos , Resistência à Doença , Isoxazóis/química , Isoxazóis/farmacologia , Estrutura Molecular , Tabaco/metabolismo , Tabaco/virologia , Vírus do Mosaico do Tabaco/efeitos dos fármacos
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