Anti-tobacco Mosaic Virus Research Articles

Brusatol's anticancer activity and its molecular mechanism: a research update.

Brusatol (BT) is a quassinoid compound extracted from Brucea javanica that is a traditional Chinese herbal medicine. Brusatol possesses biological and medical activity, including antitumor, antileukemia, anti-inflammatory, antitrypanosomal, antimalarial, and antitobacco mosaic virus activity. To summarize and discuss the antitumor effects of BT and its mechanisms of actions, we compiled this review by combining the extensive relevant literature and our previous studies. We searched and retrieved the papers that reported the pharmacological effects of BT and the mechanism of BT antitumor activity from PubMed until July 2023. Numerous studies have shown that BT is a unique nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor that acts on various signaling pathways and has good antitumor properties. Brusatol shows great potential in cancer therapy by inhibiting cell proliferation, blocking the cell cycle, promoting tumor cell differentiation, accelerating tumor cell apoptosis, inducing autophagy, suppressing angiogenesis, inhibiting tumor invasion and metastasis, and reversing multidrug resistance. This review summarizes recent updates on the antitumor activity and molecular mechanisms of BT and provides references for future development and clinical translation of BT and its derivatives as antitumor drugs.

Myricetin derivatives containing the benzoxazinone moiety discovered as potential anti-tobacco mosaic virus agents

A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X-ray diffraction analysis. The test results of EC50 values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC50 values of 236.8, 206.0 μg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 μg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (Kd) value of 0.045 μM, which was superior to the ningnanmycin (0.700 μM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents.

Antiviral Activity of Ailanthone from Ailanthus altissima on the Rice Stripe Virus.

Rice stripe disease caused by the rice stripe virus (RSV), which infects many Poaceae species in nature, is one of the most devastating plant viruses in rice that causes enormous losses in production. Ailanthone is one of the typical C20 quassinoids synthesized by the secondary metabolism of Ailanthus altissima, which has been proven to be a biologically active natural product with promising prospects and great potential for use as a lead structure for pesticide development. Based on the achievement of the systemic infection and replication of RSV in Nicotiana benthamiana plants and rice protoplasts, the antiviral properties of Ailanthone were investigated by determining its effects on viral-coding RNA gene expression using reverse transcription polymerase chain reaction, and Western blot analysis. Ailanthone exhibited a dose-dependent inhibitory effect on RSV NSvc3 expression in the assay in both virus-infected tobacco plants and rice protoplasts. Further efforts revealed a potent inhibitory effect of Ailanthone on the expression of seven RSV protein-encoding genes, among which NS3, NSvc3, NS4, and NSvc4 are the most affected genes. These facts promoted an extended and greater depth of understanding of the antiviral nature of Ailanthone against plant viruses, in addition to the limited knowledge of its anti-tobacco mosaic virus properties. Moreover, the leaf disc method introduced and developed in the study for the detection of the antiviral activity of Ailanthone facilitates an available and convenient screening method for anti-RSV natural products or synthetic chemicals.

Design, synthesis, and anti–tobacco mosaic virus activity evaluation of quinazolinone derivatives containing purine moieties

In this study, a series of quinazolinone derivatives containing purine molecules were designed and synthesized, and their structures were characterized by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and HRMS (High Resolution Mass Spectrometer). Antiviral bioassays against plant viruses indicated that some target compounds exhibited higher in vivo antiviral activity against tobacco mosaic virus (TMV) than the commercial drug ribavirin. At a concentration of 500 mg/L, compound A2 exhibited good activity against TMV, with therapeutic and protective activity values of 65.2 % and 60.2 %, respectively, and these values were superior to those of ribavirin (50.1 % and 57.2 %, respectively). Among these compounds, A2 demonstrated significant therapeutic bioactivity against TMV in vivo, with an EC50 (half-maximum effective concentration) value of 162.3 mg/L, which was superior to that of ribavirin (314.4 mg/L). In conclusion, quinazolinone derivatives containing purine molecules may provide a basis for further research on antiviral drugs.

Three new flavones from the whole plants of Cassia auriculata Linn. and their antiviral activities

Cassia auriculata, a widely grown medicinal plant in China, has not been fully studied in terms of its secondary metabolites. In our pursuit of new bioactive metabolites from Cassia plants, we conducted a phytochemical reinvestigation on C. auriculata. This investigation resulted in the isolation of three new (1−3) and six known (4−9) flavones. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Interestingly, Compounds 1-3 are rare flavones bearing an unusual (4-methylfuran-2-yl)methyl moiety. In addition, Compounds 1-3 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that Compounds 1–3 exhibited potential anti-TMV activities with inhibition rates of 26.8%, 30.5% and 34.6% at a concentration of 20 μM, respectively, and these rates are close to that of the positive control. Compounds 1-9 were also tested for their anti-rotavirus activities. The results revealed that 1–9 exhibited potential anti-rotavirus activity with therapeutic index (TI) values in the range of 13.3–20.8. These values are lower than that of the positive control (with a therapeutic index of 23.4).

Five quinolizidine alkaloids with anti-tobacco mosaic virus activities from two species of Sophora

Three novel matrine-type alkaloids (1–3) and two unprecedented aloperine-type alkaloids (4 and 5) were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively. Notably, compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton, while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system respectively. Moreover, compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core, and compound 5 characterized by rare 6/6/6/6 tetracyclic skeleton. Their structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Biological tests indicated that compound 5 displayed significant anti-tobacco mosaic virus (TMV) activity compared with the positive control ningnanmycin.

Limonene anti-TMV activity and its mode of action

The main component of orange peel essential oil is limonene. Limonene is a natural active monoterpene with multiple functions, such as antibacterial, antiseptic and antitumor activity, and has important development value in agriculture. This study found that limonene exhibited excellent anti-tobacco mosaic virus (TMV) bioactivity, with results showing that its protection activity, inactivation activity, and curative activity at 800 μg/mL were 84.93%, 59.28%, and 58.89%, respectively—significantly higher than those of chito-oligosaccharides. A direct effect of limonene on TMV particles was not observed, but limonene triggered the hypersensitive response (HR) in tobacco. Further determination of the induction activity of limonene against TMV demonstrated that it displayed good induction activity at 800 μg/mL, with a value of 60.59%. The results of physiological and biochemical experiments showed that at different treatment days, 800 μg/mL limonene induced the enhancement of defense enzymes activity in tobacco, including of SOD, CAT, POD, and PAL, which respectively increased by 3.2, 4.67, 4.12, and 2.33 times compared with the control (POD and SOD activities reached highest on the seventh day, and PAL and CAT activities reached highest on the fifth day). Limonene also enhanced the relative expression levels of pathogenesis related (PR) genes, including NPR1, PR1, and PR5, which were upregulated 3.84-fold, 1.86-fold and 1.71-fold, respectively. Limonene induced the accumulation of salicylic acid (SA), and increased the relative expression levels of genes related to SA biosynthesis (PAL) and reactive oxygen species (ROS) burst (RBOHB), which respectively increased by 2.76 times and 4.23 times higher than the control. Systemic acquired resistance (SAR) is an important plant immune defense against pathogen infection. The observed accumulation of SA, the enhancement of defense enzymes activity and the high-level expression of defense-related genes suggested that limonene may induce resistance to TMV in tobacco by activating SAR mediated by the SA signaling pathway. Furthermore, the experimental results demonstrated that the expression level of the chlorophyll biosynthesis gene POR1 was increased 1.72-fold compared to the control in tobacco treated with 800 μg/mL limonene, indicating that limonene treatment may increase chlorophyll content in tobacco. The results of pot experiment showed that 800 μg/mL limonene induced plant resistance against Sclerotinia sclerotiorum (33.33%), Phytophthora capsici (54.55%), Botrytis cinerea (50.00%). The bioassay results indicated that limonene provided broad-spectrum and long-lasting resistance to pathogen infection. Therefore, limonene has good development and utilization value, and is expected to be developed into a new botanical-derived anti-virus agent and plant immunity activator in addition to insecticides and fungicides.

C-Alkylated flavonoids from the whole plants of Desmodium caudatum and their anti-TMV activity.

Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 μg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.

Design, synthesis, and antiviral activities evaluation of novel quinazoline derivatives containing sulfonamide moiety

Abstract A series of novel quinazoline derivatives bearing sulfonamide moiety was designed and synthesized, and their structure were characterized by 1H NMR, 13C NMR, and HRMS techniques. Among them, the structure of compound E1 was further confirmed through X-ray single-crystal diffraction analyses. Their anti-Tobacco mosaic virus (TMV) activities were evaluated through half-leaf method. The bioassay results showed that E8 and E19 possess excellent inhibitory activity towards TMV. The EC50 of curative activities, protective activities, and inactivating activities of E8 and E19 are 132.1, 152.8, 57.4 mg/L and 278.0, 165.3, 94.5 mg/L, respectively, which are far superior than Ribavirin (318.2, 201.5, 128.6 mg/L, respectively).

Antiviral activity evaluation and action mechanism of myricetin derivatives containing thioether quinoline moiety.

A variety of myricetin derivatives containing thioether quinoline moiety were designed and synthesized. Their structures of title compounds were determined by 1H NMR, 13C NMR, 19F NMR, and HRMS. Single-crystal X-ray diffraction experiments were carried out with B4. Antiviral activity indicated that some of the target compounds exhibited remarkable anti-tobacco mosaic virus (TMV) activity. In particular, compound B6 possessed significant activity. The half maximal effective concentration (EC50) value of the curative activity of compound B6 was 169.0μg/mL, which was superior to the control agent ningnanmycin (227.2μg/mL). Meanwhile, the EC50 value of the protective activity of compound B6 was 86.5μg/mL, which was better than ningnanmycin (179.2μg/mL). Microscale thermophoresis (MST) indicated that compound B6 had a strong binding capability to the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (Kd) value of 0.013μmol/L, which was superior to that of myricitrin (61.447μmol/L) and ningnanmycin (3.215μmol/L). And the molecular docking studies were consistent with the experimental results. Therefore, these novel myricetin derivatives containing thioether quinoline moiety could become potential alternative templates for novel antiviral agents.

The coat protein of tobacco mosaic virus as an anti-tobacco mosaic virus: a molecular dynamics simulation

The Coat Protein (CP) of the Tobacco Mosaic Virus (TMV) executes an important duty in the protection of virus RNA. The interaction between the virus CP and host plant proteins induces infection in the host and creates dark and light green mosaics on crops, which disturb the growth and function of the plant. The interaction between the virus CP and the modified CP, expressed in transgenic plants, causes Coat Protein-Mediated Resistance (CP-MR), which reduces virus infection in transgenic plants. In this study, a model is suggested for resistance as “stop assembly of CP” in the virus. It is based on the fact that the CP, when mutated, acts as a dead-end in virus assembly. For evaluation of the model, we investigated the effect of four mutants including CBT28I, ABT42W, ABD77R, and ABT89W complexes on plant resistance against TMV infection by molecular dynamics simulation. Previous studies had shown the influence of such mutations on the CP-MR. The MD results of in the present study further confirmed the mentioned effect and demonstrated how the mutations could be the cause of CP-MR. The results are calculated by the RMSD, Rg, H-bond, and g-MMPBSA scripts. The change in binding energy between two chains is consistent with CP-MR such that with increase in binding energy, the affinity between two chains was reduced and the CP-MR increased. Based on this model, it is possible to design mutants with a high level of efficiency.Communicated by Ramaswamy H. Sarma

Design, synthesis, bioactivity and mechanism of action of novel myricetin derivatives containing amide and hydrazide

A series of myricetin derivatives containing amide and hydrazide were designed and synthesized. All the compounds were characterized by NMR and HRMS. Bioactivity test showed that some of the target compounds had excellent anti-tobacco mosaic virus (TMV) activity. In particular, the median effective concentration (EC50) values of the anti-TMV curative and protective activities of N-(2-(2-(2-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)acetyl)hydrazineyl)-2-oxoethyl)-4-(trifluoromethyl)benzamide (G9) were 202.3 and 164.0 μg/mL respectively, superior to ningnanmycin (329.1, 230.3 μg/mL). Microscale thermophoresis (MST) and molecular docking showed that G9 had an excellent binding affinity with tobacco mosaic virus coat protein (TMV-CP) (Kd = 0.158 ± 0.024 μM), which was better than that of ningnanmycin (Kd = 2.074 ± 0.818 μM). Moreover, there were many interaction forces between G9 and the key amino acid residues of TMV-CP. The chlorophyll content and peroxidase (POD) activity of tobacco leaves treated with G9 increased significantly, indicating that G9 could improve the photosynthesis of tobacco leaves and stimulate the resistance of tobacco leaves to TMV. The insecticidal activity of G9 against Mythimna separata (M. separate) was found to be 95.2% at 200 μg/mL, which was close to bufenozide (100%). The insecticidal activity of myricetin was significantly improved after the introduction of active groups of amide and hydrazide, which could be further explored.

Anti-Tobacco Mosaic Virus Indole Alkaloids from the Nicotiana tabacum-Derived Fungus Aspergillus versicolor

To explore the active metabolites from Aspergillus, we have discovered five undescribed tricyclic or tetracyclic indole alkaloids aspergillines K–O (1–5) and four known analogues (6–9) from the strain of Nicotiana tabacum-derived Aspergillus versicolor YNCA0363. The α-amino group derived from tryptophan in isolates 1–6 was changed to an oxygen atom, which is uncommon in the reported analogues. To the best of our knowledge, 4 and 5 represent the first examples of indole alkaloids possessing an isochromene moiety. Compounds 1 and 3 showed obvious anti-tobacco mosaic virus (TMV) activities with inhibition rates of 43.6% ± 2.2 and 58.5% ± 2.8 at the concentration of 20 μM, respectively, which were significantly higher than that of the positive control. Compound 3 also showed excellent potential of inducing systemic acquired resistance. Furthermore, compound 3 can increase the activities of two reactive oxygen species-scavenging enzymes, peroxidase and superoxide dismutase, and enhance tobacco resistance to TMV. Molecular docking results showed that compound 3 exhibits a stronger interaction with TMV-helicase, and showed higher antiviral activities than others. This work revealed that the above indole alkaloids, especially 3, could induce resistance in tobacco plants against the viral pathogen TMV.

Design, Synthesis, and Biological Evaluation of Novel 1,4-Pentadien-3-one Derivatives Containing a Sulfonamide Moiety

Novel 1,4-pentadien-3-one derivatives containing a sulfonamide moiety were synthesized, and their antifungal, antibacterial, and antiviral activities were verified. These compounds exhibited better activity against five bacteria, with EC50 values ranging from 9.6 to 60.1 μg/mL, prominently, which are superior to those of the commercial agent. A great amount of compounds had excellent fungicidal activity in vitro at 100 μg/mL. Strikingly, compound E6 exhibited moderate activity against Phytophthora litchii than azoxystrobin, with the EC50 value of compound E6 (0.5 μg/mL) drawing near azoxystrobin (0.3 μg/mL). Furthermore, compound E17 had a marked impact on in vivo anti-tobacco mosaic virus, according to the data of microscale thermophoresis, with a Kd value of the intermolecular binding force of 0.002 ± 0.001 μM, which was better than the commercial agent of ningnanmycin (Kd = 0.121 ± 0.031 μM). In addition, the results of these studies suggest that the use of active splicing can improve the biological activity of natural compounds and provide further complement to the development of novel pesticides.

Structural Optimization of the Natural Product: Discovery of Almazoles C–D and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents

Plant diseases seriously affect the growth of crops and the quality and yield of agricultural products. The search for plant-derived pesticide candidates based on natural products is a hot topic of current research. Marine natural products almazoles C-D were efficiently prepared and selected as the lead compounds in this work. Two series of almazole derivatives were designed and synthesized, and their antiviral and fungicidal activities were systematically evaluated. The results of anti-tobacco mosaic virus (anti-TMV) activity showed that almazoles C-D and their derivatives had good anti-TMV activities. Compounds 6, 15, 16a, 16b, 16g, 16l, 16n, 20a, 20d, 20i, and 20n exhibited better anti-TMV activities than the commercial antiviral agent ribavirin. Anti-TMV mechanism studies showed that compound 16b could induce the polymerization of 20S CP (coat protein, CP), thereby affecting the assembly of TMV virus particles. Molecular docking results showed that compounds 15, 16b, and 20n could combine with amino acid residues through hydrogen bonds to achieve an excellent anti-TMV effect. In addition, most of the almazole derivatives were found to have broad-spectrum fungicidal activities against eight kinds of plant pathogens (Fusarium oxysporum f. sp. cucumeris, Cercospora arachidicola Hori, Physalospora piricola, Rhizoctonia cerealis, Alternaria solani, Pyricularia grisea, Phytophthora capsici, and Sclerotinia sclerotiorum). This study provides an important evidence for the research and development of almazole alkaloids containing indole and oxazole structural groups as novel agrochemicals.

Synthesis and Evaluation of 11-Butyl Matrine Derivatives as Potential Anti-Virus Agents.

Matrine derivatives were reported to have various biological activities, especially the ester, amide or sulfonamide derivatives of matrine deriving from the hydroxyl or carboxyl group at the end of the branch chain after the D ring of matrine is opened. In this work, to investigate whether moving away all functional groups from the C-11 branch chain could have an impact on the bioactivities, such as anti-tobacco mosaic virus (TMV), insecticidal and fungicidal activities, a variety of N-substituted-11-butyl matrine derivatives were synthesized. The obtained bioassay result showed that most N-substituted-11-butyl matrine derivatives had obviously enhanced anti-TMV activity compared with matrine, especially many compounds had good inhibitory activity close to that of commercialized virucide Ningnanmycin (inhibition rate 55.4, 57.8 ± 1.4, 55.3 ± 0.5 and 60.3 ± 1.2% at 500 μg/mL; 26.1, 29.7 ± 0.2, 24.2 ± 1.0 and 27.0 ± 0.3% at 100 μg/mL, for the in vitro activity, in vivo inactivation, curative and protection activities, respectively). Notably, N-benzoyl (7), N-benzyl (16), and N-cyclohexylmethyl-11-butyl (19) matrine derivatives had higher anti-TMV activity than Ningnanmycin at both 500 and 100 μg/mL for the four test modes, showing high potential as anti-TMV agent. Furthermore, some compounds also showed good fungicidal activity or insecticidal activity.

Antitobacco Mosaic Virus Activity of a New Eremophilane Glucoside From the Leaves of Nicotiana tabacum L

A new eremophilane-type sesquiterpene glucoside, 13-hydroxycapsidiol 3- O- β-D-glucoside (1), was isolated from the leaves of Nicotiana tabacum L. The structure of this new metabolite was determined by one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and comparison with values reported in the literature. Compound 1 was the second glycosylated eremophilane sesquiterpenoid isolated from plants of the Solanaceae family and exhibited a more potent anti-tobacco mosaic virus (anti-TMV) activity, with an inhibition rate of 39.4% at 20 μM, than the positive control ningnanmycin (34.8%).

Anti-Tobacco Mosaic Virus Effects of Silver Nanoparticles Coated with Alginate Oligosaccharides Prepared through Enzymatic Degradation

Recombinant alginate lyase was used to degrade alginic acid to prepare unsaturated alginate oligosaccharides (AOs), which were applied to directly reduce silver nitrate to obtain AO-coated silver nanoparticles (AOs@AgNPs), and as a stabilizer as well. First, alginate lyase aly-SJ02 from the marine bacterium Pseudoalteromonas sp. SM0524 was heterologously expressed in Yarrowia lipolytica. Next, the AOs produced through enzymatic degradation were used as reducing and stabilizing agents with silver nitrate to prepare AOs@AgNPs, and the particle size, stability, and other basic data were measured. Finally, based on the enhancement of plant resistance by AOs and the broad-spectrum antiviral bactericidal effect, three kinds of AgNPs had desirable passivation, prevention, and treatment effects on tobacco mosaic virus (TMV). The best control effect was observed for AOs@AgNPs, and it has been verified that AOs@AgNPs have a strong inhibitory effect at both the gene transcription and protein expression levels of TMV. AOs@AgNPs were far better than the AgNPs prepared by using alginate polysaccharides.

Maillard Reaction Products with Anti-Tobacco Mosaic Virus Activities Generated in Processed Thermopsis lanceolata R. Br. Seed Extract.

Six novel Maillard reaction products (MRPs) (1-6) were isolated from the processed Thermopsis lanceolata R. Br. seed extract, along with one biogenetically related intermediate (7). Compounds 1-4 possessed three rare dimerization patterns constructed by cytisine, whereas compounds 5 and 6 represented the first example of the addition products of cytisine and 5,6-dihydroxy-4-hexanolide. Their structures were elucidated by comprehensive spectroscopic data analysis and quantum chemistry calculations including GIAO 13C{1H} NMR and ECD calculation, combined with single-crystal X-ray diffraction analysis. Biologically, compound 3 displayed significant anti-tobacco mosaic virus activity compared with the positive control ningnanmycin.

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

In previous studies, several isoindolin-1-one analogs that exhibited significant anti-tobacco mosaic virus (anti-TMV) activities were isolated from Nicotiana tabacum. Since gene-editing mutants provide a new sample for the discovery of active metabolites, we focused on the stems of YN-18-23 (a mutant N. tabacum for gene editing with the alkaloid metabolic pathway cultivated by Yunnan Tobacco Company), which led to the isolation of four new (1-4) and four known (5-8) isoindolin-1-ones. To the best of our knowledge, nicindole C (3) is the first subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D (4) is the first example of isoindolin-1-one bearing a methyl-pyridin-2-(1H)-one moiety. Compounds 1-4 were tested for their anti-TMV activities, and the results revealed that compounds 1, 3, and 4 exhibited high anti-TMV activities at concentrations of 20μM with inhibition rates of 48.6, 42.8, and 71.5%, respectively. These rates are higher than the inhibition rate of the positive control (33.2%). The mechanistic study of compound 4, which had the highest anti-TMV activity revealed that increased potentiation of defense-related enzyme activities and downregulation of expression of the NtHsp70 protein may induce resistance in tobacco against the viral pathogen TMV. Molecular docking studies also revealed that the isoindolin-1-one substructure is fundamental for anti-TMV activity. The methyl-pyridin-2-(1H)-one moiety in compound 4 and the 2-oxopropyl groups in compounds 1 and 3 at the N-2 position may increase inhibitory activities. This study of the structure-activity relationship is helpful for finding new anti-TMV activity inhibitors. To study whether the isoindolin-1-ones have broader antiviral activities, compounds 1-4 were also tested for their anti-rotavirus activities. Compound 4 exhibited high anti-rotavirus activity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).