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1.
J Agric Food Chem ; 68(50): 15015-15026, 2020 Dec 16.
Article in English | MEDLINE | ID: mdl-33285067

ABSTRACT

The discovery of novel, effective, and botanical pesticides is one of the main strategies for modern plant protection and insect pest control. During the search for novel botanical pesticides from natural sources, the seeds of Sophora tonkinensis were systematically investigated to obtain 11 new matrine-type alkaloids (1-11), including one novel matrine-type alkaloid featuring an unprecedented 5/6/6/6 tetracyclic skeleton (1), along with 16 known compounds (12-27). Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HRESIMS), ECD calculations, and single-crystal X-ray diffraction. The anti-tobacco mosaic virus (TMV) activity and insecticidal activities against Aphis fabae and Tetranychus urticae of the compounds were also respectively screened using the half-leaf method and spray method. Biological tests indicated that compounds 2, 4, 6, and 26 displayed significant anti-TMV biological activities compared with the positive control ningnanmycin. Compounds 7, 17, and 26 presented moderate activities against A. fabae with LC50 values of 38.29, 18.63, and 23.74 mg/L, respectively. Moreover, compounds 13 and 26 exhibited weak activities against T. urticae.


Subject(s)
Alkaloids/pharmacology , Antiviral Agents/pharmacology , Insecticides/pharmacology , Plant Extracts/pharmacology , Quinolizidines/pharmacology , Sophora/chemistry , Alkaloids/chemistry , Animals , Antiviral Agents/chemistry , Insecta/drug effects , Insecta/growth & development , Insecticides/chemistry , Plant Extracts/chemistry , Quinolizidines/chemistry , Seeds/chemistry , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
2.
J Agric Food Chem ; 68(44): 12241-12251, 2020 Nov 04.
Article in English | MEDLINE | ID: mdl-33103899

ABSTRACT

Globally, the citrus industry produces various wastes, which contain a great deal of limonoids. In order for the sustainable development of the citrus industry, and considering the diverse bioactivities of limonoids, a series of ester derivatives were constructed by structural modification of limonin in the B ring. Furthermore, two seven-membered lactone derivatives of limonin and obacunone with a novel skeleton in the B ring were obtained by the Baeyer-Villiger oxidation rearrangement. The steric structures of six key compounds 3a, 3b, 4m, 4n, 6, and 7 were determined by X-ray crystallography. It demonstrated that the molar ratio of 3a (7α-isomer) and 3b (7ß-isomer) depended on the mixed solvents in the reduction system. The anti-tobacco mosaic virus (TMV) activities under three different modes of action for most of the tested compounds were as the following sequence: inactivation effect > protection effect > curative effect. It was noteworthy that compound 4aa displayed the most potent anti-TMV/insect growth inhibitory activities, which indicated that the introduction of the phenylacryloyloxy group at the C-7ß position of limonin could significantly improve its agricultural biological activities. This study will pave the way for future value-added application of citrus industrial wastes and provide strong evidence for the discovery of sustainable biopesticides based on limonoids.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Citrus/chemistry , Insecticides/chemical synthesis , Insecticides/pharmacology , Tobacco Mosaic Virus/drug effects , Agriculture , Animals , Antiviral Agents/chemistry , Industrial Waste/analysis , Insecta/drug effects , Insecta/growth & development , Insecticides/chemistry , Molecular Structure , Tobacco Mosaic Virus/growth & development , Waste Products/analysis
3.
J Agric Food Chem ; 68(41): 11350-11357, 2020 Oct 14.
Article in English | MEDLINE | ID: mdl-32956590

ABSTRACT

Plant diseases are seriously endangering agricultural production. The emergence of drug resistance has brought great challenges to the prevention and control of plant diseases. There is an urgent need for the emergence of new drug candidates. In this work, we achieved the efficient synthesis of pulmonarins A and B in 64% and 59% overall yield, respectively. Pulmonarins A and B were found to have good antiviral activities against tobacco mosaic virus (TMV) for the first time. A series of pulmonarin derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities systematically. Most compounds displayed higher anti-TMV activities than commercial ribavirin. Compounds 6a, 6c, and 6n with better inactivation effects than ningnanmycin emerged as new antiviral candidates. We selected 6c for further antiviral mechanism research, which revealed that it could inhibit virus assembly by interacting with TMV coat protein (CP). The molecular docking results further confirmed that these compounds could interact with CP through hydrogen bonding. These compounds also displayed broad spectrum fungicidal activities. Especially compound 6u with prominent antifungal activity emerged as a new fungicidal candidate for further research. The current work provides a reference for understanding the application of pulmonarin alkaloids in plant protection.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Bromobenzenes/pharmacology , Fungicides, Industrial/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Bromobenzenes/chemical synthesis , Bromobenzenes/chemistry , Fungi/drug effects , Fungi/growth & development , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Molecular Docking Simulation , Plant Diseases/microbiology , Plant Diseases/virology , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
4.
Food Environ Virol ; 12(3): 269-273, 2020 09.
Article in English | MEDLINE | ID: mdl-32666473

ABSTRACT

Monthly sampling was conducted at a drinking water treatment plant (DWTP) in Southern Louisiana, USA from March 2017 to February 2018 to determine the prevalence and reduction efficiency of pathogenic and indicator viruses. Water samples were collected from the DWTP at three different treatment stages (raw, secondary-treated, and chlorinated drinking water) and subjected to quantification of seven pathogenic viruses and three indicator viruses [pepper mild mottle virus (PMMoV), tobacco mosaic virus (TMV), and crAssphage] based on quantitative polymerase chain reaction. Among the seven pathogenic viruses tested, only Aichi virus 1 (AiV-1) (7/12, 58%) and noroviruses of genogroup II (NoVs-GII) (2/12, 17%) were detected in the raw water samples. CrAssphage had the highest positive ratio at 78% (28/36), and its concentrations were significantly higher than those of the other indicator viruses for all three water types (P < 0.05). The reduction ratios of AiV-1 (0.7 ± 0.5 log10; n = 7) during the whole treatment process were the lowest among the tested viruses, followed by crAssphage (1.1 ± 1.9 log10; n = 9), TMV (1.3 ± 0.9 log10; n = 8), PMMoV (1.7 ± 0.8 log10; n = 12), and NoVs-GII (3.1 ± 0.1 log10; n = 2). Considering the high abundance and relatively low reduction, crAssphage was judged to be an appropriate process indicator during drinking water treatment. To the best of our knowledge, this is the first study to assess the reduction of crAssphage and TMV during drinking water treatment.


Subject(s)
Drinking Water/virology , Enterovirus/growth & development , Kobuvirus/growth & development , Tobacco Mosaic Virus/growth & development , Tobamovirus/growth & development , Enterovirus/genetics , Enterovirus/isolation & purification , Kobuvirus/genetics , Kobuvirus/isolation & purification , Tobacco Mosaic Virus/genetics , Tobacco Mosaic Virus/isolation & purification , Tobamovirus/genetics , Tobamovirus/isolation & purification , Water Pollution/analysis , Water Purification
5.
J Agric Food Chem ; 68(30): 7839-7849, 2020 Jul 29.
Article in English | MEDLINE | ID: mdl-32649198

ABSTRACT

Plant diseases caused by plant viruses and pathogens seriously affect the production and storage of food crops. With the emergence of drug resistance, it is very difficult to control. Natural products are the source of new drug discovery. Here, the natural product streptindole was found to have good antiviral activity against tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi. A series of derivatives of streptindole were designed, synthesized, and evaluated for their antiviral and fungicidal activities. Compounds 4, 5, 11, 12c, 12d, 13d, and 13i-13l showed higher anti-TMV activities than ribavirin (inhibitory rate: 38, 37, and 40% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively), among which compound 12d (inhibitory rate: 57, 55, and 53% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity was further evaluated for the mode of action. The mechanism research revealed that 12d can break the three-dimensional structure of TMV coat protein (CP) through hydrogen bonds, thus inhibiting the assembly of virus particles. The molecular docking result showed that compound 12d did exhibit strong interaction with TMV CP. The derivatives of streptindole also displayed broad-spectrum fungicidal activities. The current study provided valuable insights into the antiviral and fungicidal activities of streptindole derivatives.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/pharmacology , Fungi/drug effects , Fungi/growth & development , Molecular Docking Simulation , Plant Diseases/microbiology , Plant Diseases/virology , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
6.
Food Environ Virol ; 12(3): 260-263, 2020 09.
Article in English | MEDLINE | ID: mdl-32613519

ABSTRACT

This study assessed wastewater quality through the quantification of four human enteric viruses and the applicability of pepper mild mottle virus (PMMoV) and tobacco mosaic virus (TMV) as indicators of viral reduction during wastewater treatment. Thirty-three samples were collected from three steps of a wastewater treatment plant in Southern Louisiana, USA for a year between March 2017 and February 2018. Noroviruses of genogroup I were the most prevalent human enteric viruses in influent samples. The concentrations of PMMoV in influent samples (5.9 ± 0.7 log10 copies/L) and biologically treated effluent samples (5.9 ± 0.5 log10 copies/L) were significantly higher than those of TMV (P < 0.05), and the reduction ratio of PMMoV (1.0 ± 0.8 log10) was found comparable to those of TMV and Aichi virus 1. Because of the high prevalence, high correlations with human enteric viruses, and lower reduction ratios, PMMoV was deemed an appropriate indicator of human enteric viral reduction during wastewater treatment process.


Subject(s)
Enterovirus/isolation & purification , Tobacco Mosaic Virus/isolation & purification , Tobamovirus/isolation & purification , Wastewater/virology , Water Purification/methods , Enterovirus/classification , Enterovirus/genetics , Enterovirus/growth & development , Humans , Louisiana , Sewage/virology , Tobacco Mosaic Virus/genetics , Tobacco Mosaic Virus/growth & development , Tobamovirus/genetics , Tobamovirus/growth & development , Water Purification/instrumentation
7.
J Agric Food Chem ; 68(27): 7226-7234, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32530620

ABSTRACT

A series of novel α-ketoamide derivatives bearing a vanillin skeleton were designed and synthesized. Bioactivity tests on virus and bacteria were performed. The results indicated that some compounds exhibited excellent antitobacco mosaic virus (TMV) activities, such as compound 34 exhibited an inactivation activity of 90.1% and curative activity of 51.8% and compound 28 exhibited a curative activity of 54.8% at 500 µg mL-1, which is equivalent to that of the commercial ningnanmycin (inactivation of 91.9% and curative of 51.9%). Moreover, the in vitro antibacterial activity test illustrated that compounds 2, 22, and 33 showed much higher activities than commercial thiodiazole copper, which could be used as lead compounds or potential candidates. The findings of transmission electron microscopy and molecular docking indicated that the synthesized compounds exhibited strong and significant binding affinity to the TMV coat protein and could obstruct the self-assembly and increment of TMV particles. This study revealed that α-ketoamide derivatives bearing a vanillin skeleton could be used as a novel potential pesticide for controlling the plant diseases.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Benzaldehydes/chemistry , Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Bacteria/drug effects , Bacteria/growth & development , Benzaldehydes/pharmacology , Drug Design , Microbial Sensitivity Tests , Molecular Docking Simulation , Plant Diseases/microbiology , Plant Diseases/virology , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
8.
J Agric Food Chem ; 68(20): 5586-5595, 2020 May 20.
Article in English | MEDLINE | ID: mdl-32357298

ABSTRACT

Plant diseases seriously affect the yield and quality of crops and are difficult to control. Tryptanthrin and its derivatives (tryptanthrins) were synthesized and evaluated for their antiviral activities and fungicidal activities. We found that tryptanthrins have good antiviral activities against tobacco mosaic virus (TMV) for the first time. Most of the tryptanthrins showed higher anti-TMV activities than that of ribavirin (inhibitory rates of 40, 37, and 38% at 500 µg/mL for inactivation, curative, and protection activities in vivo, respectively). Compound 3n (inhibitory rates of 52, 49, and 54% at 500 µg/mL for inactivation, curative, and protection activities in vivo, respectively) and compound 14 (inhibitory rates of 51, 48, and 53% at 500 µg/mL for inactivation, curative, and protection activities in vivo, respectively) emerged as new antiviral lead compounds with excellent antiviral activities. Compound 16 was selected for further antiviral mechanism research, which revealed that compound 16 could inhibit virus assembly by decomposing 20S coat protein (CP) disk. Molecular docking results showed that compounds 3n and 14, which have higher antiviral activities in vivo than that of compound 16, do show stronger interaction with TMV CP. Further fungicidal activity tests showed that tryptanthrins displayed broad-spectrum fungicidal activities, especially for compound 16. These compounds showed good selectivity to Physalospora piricola. In the current study, a small molecular library of tryptanthrin was constructed and the bioactivity spectrum of these compounds was broadened, which lays a foundation for their application in plant protection.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/pharmacology , Quinazolines/pharmacology , Drug Design , Fungi/drug effects , Fungi/growth & development , Molecular Docking Simulation , Molecular Structure , Plant Diseases/microbiology , Plant Diseases/virology , Quinazolines/chemistry , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
9.
J Agric Food Chem ; 68(20): 5555-5571, 2020 May 20.
Article in English | MEDLINE | ID: mdl-32343564

ABSTRACT

On the basis of the mechanism of acylhydrazone compounds inhibiting the assembly of TMV CP and the unique structural characteristics of diketopiperazine ring, a series of optically pure indole diketopiperazine acylhydrazone were designed and synthesized. In order to systematically study the effect of the spatial configuration of the compounds on the antiviral activity, four compounds with different spatial configurations at C6 and C12a were also prepared. The bioassay results indicated that most of these new compounds displayed moderate to good antiviral activity, among which compounds 23, 25, 27, 28, 31, and 5d showed a significantly higher activity than that of commercial ribavirin. An in-depth structure-activity relationship investigation showed that the spatial conformation was one of the most important factors in adjusting antiviral activity; the research results provided information about the possible optimum configuration for interaction of this molecular with its target protein. At the same time, these new compounds also exhibited broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. What's more, some of these compounds exhibited good insecticidal activity to Plutella xylostella and Culex pipiens pallens.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/pharmacology , Insecticides/chemical synthesis , Insecticides/pharmacology , Animals , Antiviral Agents/chemistry , Culex/drug effects , Culex/growth & development , Diketopiperazines/chemistry , Diketopiperazines/pharmacology , Drug Design , Fungi/drug effects , Fungi/growth & development , Fungicides, Industrial/chemistry , Hydrazones/chemistry , Hydrazones/pharmacology , Indoles/chemistry , Indoles/pharmacology , Insecticides/chemistry , Lepidoptera/drug effects , Lepidoptera/growth & development , Molecular Structure , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
10.
Sci Rep ; 10(1): 3616, 2020 02 27.
Article in English | MEDLINE | ID: mdl-32107444

ABSTRACT

This study was conducted to evaluate the applicability of crAssphage, pepper mild mottle virus (PMMoV), and tobacco mosaic virus (TMV) as indicators of the reduction of human enteric viruses during wastewater treatment. Thirty-nine samples were collected from three steps at a wastewater treatment plant (raw sewage, secondary-treated sewage, and final effluent) monthly for a 13-month period. In addition to the three indicator viruses, eight human enteric viruses [human adenoviruses, JC and BK polyomaviruses, Aichi virus 1 (AiV-1), enteroviruses, and noroviruses of genogroups I, II, and IV] were tested by quantitative PCR. Indicator viruses were consistently detected in the tested samples, except for a few final effluents for crAssphage and TMV. The mean concentrations of crAssphage were significantly higher than those of most tested viruses. The concentrations of crAssphage in raw sewage were positively correlated with the concentrations of all tested human enteric viruses (p <0.05), suggesting the applicability of crAssphage as a suitable indicator to estimate the concentrations of human enteric viruses in raw sewage. The reduction ratios of AiV-1 (1.8 ± 0.7 log10) were the lowest among the tested viruses, followed by TMV (2.0 ± 0.3 log10) and PMMoV (2.0 ± 0.4 log10). Our findings suggested that the use of not only AiV-1 and PMMoV but also TMV as indicators of reductions in viral levels can be applicable during wastewater treatment.


Subject(s)
Enterovirus/growth & development , Tobacco Mosaic Virus/growth & development , Tobamovirus/growth & development , Wastewater/virology , Enterovirus/genetics , Enterovirus/isolation & purification , Sewage/virology , Tobacco Mosaic Virus/genetics , Tobacco Mosaic Virus/isolation & purification , Tobamovirus/genetics , Tobamovirus/isolation & purification , Water Pollution/analysis , Water Purification
11.
J Agric Food Chem ; 68(9): 2631-2638, 2020 Mar 04.
Article in English | MEDLINE | ID: mdl-32023057

ABSTRACT

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.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Harmine/chemistry , Harmine/pharmacology , Plant Viruses/drug effects , Tobacco Mosaic Virus/drug effects , Antiviral Agents/chemical synthesis , Drug Design , Harmine/chemical synthesis , Isomerism , Molecular Conformation , Plant Diseases/virology , Plant Viruses/growth & development , Structure-Activity Relationship , Tobacco Mosaic Virus/growth & development
12.
J Agric Food Chem ; 67(48): 13344-13352, 2019 Dec 04.
Article in English | MEDLINE | ID: mdl-31721573

ABSTRACT

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.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Diamide/chemistry , Hydrazones/chemistry , Plant Viruses/drug effects , Pyridines/chemistry , Antiviral Agents/chemistry , Cucumovirus/drug effects , Cucumovirus/growth & development , Diamide/pharmacology , Drug Design , Hydrazones/pharmacology , Microbial Sensitivity Tests , Plant Viruses/growth & development , Pyridines/chemical synthesis , Pyridines/pharmacology , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
13.
J Agric Food Chem ; 67(50): 13882-13891, 2019 Dec 18.
Article in English | MEDLINE | ID: mdl-31721582

ABSTRACT

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.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Indoles/pharmacology , Plant Diseases/virology , Antiviral Agents/chemistry , Drug Design , Indoles/chemistry , Potyvirus/drug effects , Potyvirus/growth & development , Structure-Activity Relationship , Nicotiana/virology , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
14.
J Agric Food Chem ; 67(36): 10018-10031, 2019 Sep 11.
Article in English | MEDLINE | ID: mdl-31448918

ABSTRACT

Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.


Subject(s)
Antiviral Agents/pharmacology , Fungicides, Industrial/pharmacology , Oxazoles/pharmacology , Thiazoles/pharmacology , Alternaria/drug effects , Alternaria/growth & development , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Drug Design , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Oxazoles/chemistry , Structure-Activity Relationship , Thiazoles/chemistry , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
15.
J Agric Food Chem ; 67(37): 10498-10504, 2019 Sep 18.
Article in English | MEDLINE | ID: mdl-31452369

ABSTRACT

Owing to the changing needs of agriculture, the exploration of new pest control agents remains as critical as ever. The analogues 3a-3v of the natural product cerbinal were synthesized from genipin by an efficient and practical method under additive-free conditions. The antiviral and insecticidal effects of cerbinal and these cyclopenta[c]pyridines (3a-3v) were evaluated systematically. Most of the synthesized compounds exhibited higher anti-TMV activities than the lead compound cerbinal. Compound 3s (2-(4-methoxyphenyl)) had the most promising inhibitory activities against TMV (inactivation effect 49.0 ± 0.8%, curative effect 41.2 ± 4.3%, and protection effect 51.5 ± 2.7% at 500 µg/mL). Among the synthesized compounds, only 3v (2-(2-chloro-4-(trifluoromethoxy)phenyl)) reached the activity level of cerbinal against Plutella xylostella. This suggested that the cyclopenta[c]pyridines obtained by modifications of cerbinal at position 2 are very significant for the anti-TMV activity, and yet were exceptionally less active for the insecticidal activities.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Biological Products/chemical synthesis , Biological Products/pharmacology , Indenes/chemistry , Indenes/pharmacology , Insecticides/chemistry , Insecticides/pharmacology , Animals , Antiviral Agents/chemistry , Biological Products/chemistry , Drug Discovery , Indenes/chemical synthesis , Insecticides/chemical synthesis , Iridoids/chemistry , Molecular Structure , Moths/drug effects , Moths/growth & development , Pyridines/chemical synthesis , Pyridines/chemistry , Pyridines/pharmacology , Structure-Activity Relationship , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
16.
Probiotics Antimicrob Proteins ; 11(4): 1370-1378, 2019 12.
Article in English | MEDLINE | ID: mdl-30887308

ABSTRACT

Antimicrobial peptides (AMPs) are generally small peptides with less than 50 amino acid residues, which have been considered as the first line of defense system in plants and animals. These small cationic peptides belong to a family of antimicrobials that are multifunctional effectors of innate immunity. The direct antimicrobial activity of AMPs against different bacteria, viruses, fungi, and parasites has been confirmed in different studies. In this study, the antiviral activity of two recombinant AMPs named thanatin and lactoferricin+lactoferrampin was evaluated against Tobacco mosaic virus (TMV) using half-leaf and leaf disk methods under in vivo and in vitro condition, respectively. The obtained result indicated that both recombinant AMPs have shown an antiviral activity against TMV. Compared to the chimeric lactoferricin+lactoferrampin, recombinant thanatin showed a higher rate of antiviral activity against TMV. Three types of effects, including protective, curative, and inactivation, were evaluated during an antiviral activity test. In the present study, the antiviral activity of two recombinant AMPs is represented for the first time: thanatin and chimeric lactoferricin+lactoferrampin against TMV as a viral plant pathogen.


Subject(s)
Antiviral Agents/pharmacology , Peptides/pharmacology , Tobacco Mosaic Virus/drug effects , Antiviral Agents/metabolism , Peptides/genetics , Peptides/metabolism , Plant Diseases/virology , Tobacco Mosaic Virus/growth & development
17.
J Agric Food Chem ; 67(11): 3168-3178, 2019 Mar 20.
Article in English | MEDLINE | ID: mdl-30799619

ABSTRACT

In this study we report a secretory protein that was purified from Serratia marcescens strain S3 isolated from soil from the tobacco rhizosphere. Subsequent mass spectrometry and annotation characterized the protein as secretory alkaline metalloprotease (SAMP). SAMP plays a crucial role in inhibiting Tobacco mosaic virus (TMV). Transmission electron microscopy (TEM), dynamic light scattering (DLS), confocal microscopy, and microscale thermophoresis (MST) were employed to investigate the anti-TMV mechanism of SAMP. Our results demonstrated that SAMP, as a hydrolytic metal protease, combined and hydrolyzed TMV coat proteins to destroy the virus particles. This study is the first to investigate the antiviral effects of a S. marcescens metalloprotease, and our finding suggests that S. marcescens-S3 may be agronomically useful as a disease-controlling factor active against Tobacco mosaic virus.


Subject(s)
Antiviral Agents/pharmacology , Bacterial Proteins/metabolism , Bacterial Proteins/pharmacology , Metalloproteases/pharmacology , Serratia marcescens/enzymology , Antiviral Agents/isolation & purification , Antiviral Agents/metabolism , Bacterial Proteins/isolation & purification , Metalloproteases/isolation & purification , Metalloproteases/metabolism , Serratia marcescens/chemistry , Serratia marcescens/genetics , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
18.
PLoS Pathog ; 14(1): e1006756, 2018 01.
Article in English | MEDLINE | ID: mdl-29293695

ABSTRACT

Plant genomes encode large numbers of nucleotide-binding (NB) leucine-rich repeat (LRR) immune receptors (NLR) that mediate effector triggered immunity (ETI) and play key roles in protecting crops from diseases caused by devastating pathogens. Fitness costs are associated with plant NLR genes and regulation of NLR genes by micro(mi)RNAs and phased small interfering RNAs (phasiRNA) is proposed as a mechanism for reducing these fitness costs. However, whether NLR expression and NLR-mediated immunity are regulated during plant growth is unclear. We conducted genome-wide transcriptome analysis and showed that NLR expression gradually increased while expression of their regulatory small RNAs (sRNA) gradually decreased as plants matured, indicating that sRNAs could play a role in regulating NLR expression during plant growth. We further tested the role of miRNA in the growth regulation of NLRs using the tobacco mosaic virus (TMV) resistance gene N, which was targeted by miR6019 and miR6020. We showed that N-mediated resistance to TMV effectively restricted this virus to the infected leaves of 6-week old plants, whereas TMV infection was lethal in 1- and 3-week old seedlings due to virus-induced systemic necrosis. We further found that N transcript levels gradually increased while miR6019 levels gradually decreased during seedling maturation that occurs in the weeks after germination. Analyses of reporter genes in transgenic plants showed that growth regulation of N expression was post-transcriptionally mediated by MIR6019/6020 whereas MIR6019/6020 was regulated at the transcriptional level during plant growth. TMV infection of MIR6019/6020 transgenic plants indicated a key role for miR6019-triggered phasiRNA production for regulation of N-mediated immunity. Together our results demonstrate a mechanistic role for miRNAs in regulating innate immunity during plant growth.


Subject(s)
Gene Expression Regulation, Plant , Immunity, Innate , Nicotiana/metabolism , Plant Immunity , RNA Interference , RNA, Small Interfering/metabolism , Solanum lycopersicum/metabolism , Disease Resistance , Gene Expression Profiling , Genes, Reporter , Genome, Plant , Solanum lycopersicum/growth & development , Solanum lycopersicum/immunology , Solanum lycopersicum/virology , NLR Proteins/genetics , NLR Proteins/metabolism , Plant Diseases/immunology , Plant Diseases/virology , Plant Leaves/growth & development , Plant Leaves/immunology , Plant Leaves/metabolism , Plant Leaves/virology , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/immunology , Plants, Genetically Modified/metabolism , Plants, Genetically Modified/virology , RNA, Plant , Seedlings/growth & development , Seedlings/immunology , Seedlings/metabolism , Seedlings/virology , Species Specificity , Nicotiana/growth & development , Nicotiana/immunology , Nicotiana/virology , Tobacco Mosaic Virus/genetics , Tobacco Mosaic Virus/growth & development , Tobacco Mosaic Virus/physiology
19.
Food Environ Virol ; 10(1): 107-120, 2018 03.
Article in English | MEDLINE | ID: mdl-29098656

ABSTRACT

Irrigation water is a doorway for the pathogen contamination of fresh produce. We quantified pathogenic viruses [human adenoviruses, noroviruses of genogroups I and II, group A rotaviruses, Aichi virus 1 (AiV-1), enteroviruses (EnVs), and salivirus (SaliV)] and examined potential index viruses [JC and BK polyomaviruses (JCPyVs and BKPyVs), pepper mild mottle virus (PMMoV), and tobacco mosaic virus (TMV)] in irrigation water sources in the Kathmandu Valley, Nepal. River, sewage, wastewater treatment plant (WWTP) effluent, pond, canal, and groundwater samples were collected in September 2014, and in April and August 2015. Viruses were concentrated using an electronegative membrane-vortex method and quantified using TaqMan (MGB)-based quantitative PCR (qPCR) assays with murine norovirus as a molecular process control to determine extraction-reverse transcription-qPCR efficiency. Tested pathogenic viruses were prevalent with maximum concentrations of 5.5-8.8 log10 copies/L, and there was a greater abundance of EnVs, SaliV, and AiV-1. Virus concentrations in river water were equivalent to those in sewage. Canal, pond, and groundwater samples were found to be less contaminated than river, sewage, and WWTP effluent. Seasonal dependency was clearly evident for most of the viruses, with peak concentrations in the dry season. JCPyVs and BKPyVs had a poor detection ratio and correspondence with pathogenic viruses. Instead, the frequently proposed PMMoV and the newly proposed TMV were strongly predictive of the pathogen contamination level, particularly in the dry season. We recommend utilizing canal, pond, and groundwater for irrigation to minimize deleterious health effects and propose PMMoV and TMV as indexes to elucidate pathogenic virus levels in environmental samples.


Subject(s)
Agricultural Irrigation , DNA Viruses/growth & development , Environmental Monitoring/methods , Plant Viruses/growth & development , RNA Viruses/growth & development , Virus Diseases/virology , Water Pollution/analysis , Adenoviridae/genetics , Adenoviridae/growth & development , Crops, Agricultural/virology , DNA Viruses/genetics , Enterovirus/genetics , Enterovirus/growth & development , Humans , Kobuvirus/genetics , Kobuvirus/growth & development , Nepal , Norovirus/genetics , Norovirus/growth & development , Plant Viruses/genetics , Polymerase Chain Reaction , RNA Viruses/genetics , Rivers/virology , Tobacco Mosaic Virus/genetics , Tobacco Mosaic Virus/growth & development , Tobamovirus/genetics , Tobamovirus/growth & development , Wastewater/virology , Water/standards
20.
Virology ; 510: 76-89, 2017 10.
Article in English | MEDLINE | ID: mdl-28710959

ABSTRACT

In this study we use vascular specific promoters and a translating ribosome affinity purification strategy to identify phloem associated translatome responses to infection by tobacco mosaic virus (TMV) in systemic hosts Arabidopsis thaliana ecotype Shahdara and Nicotiana benthamiana. Results demonstrate that in both hosts the number of translatome gene alterations that occurred in response to infection is at least four fold higher in phloem specific translatomes than in non-phloem translatomes. This finding indicates that phloem functions as a key responsive tissue to TMV infection. In addition, host comparisons of translatome alterations reveal both similarities and differences in phloem responses to infection, representing both conserved virus induced phloem alterations involved in promoting infection and virus spread as well as host specific alterations that reflect differences in symptom responses. Combined these results suggest phloem tissues play a disproportion role in the mediation and control of host responses to virus infection.


Subject(s)
Arabidopsis/virology , Host-Pathogen Interactions , Nicotiana/virology , Phloem/virology , Protein Biosynthesis , Tobacco Mosaic Virus/growth & development , Arabidopsis/genetics , Arabidopsis/metabolism , Nicotiana/genetics , Nicotiana/metabolism
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