Bio-control of soil-borne virus infection by seed application of Glycyrrhiza glabra extract and the rhamnolipid Rhapynal.

MAIN CONCLUSION: Seed-application of the natural products protects sugar beet and wheat plants against infection with plasmodiophorid-transmitted viruses and thus may represent an efficient, environmentally friendly, easy and cost effective biocontrol strategy. In times of intensive agriculture, resource shortening and climate change, alternative, more sustainable and eco-friendly plant protection strategies are required. Here, we tested the potential of the natural plant substances Glycyrrhiza glabra leaf extract (GE) and the rhamnolipid Rhapynal (Rha) applied to seeds to protect against infection of sugar beet and wheat with soil-borne plant viruses. The soil-borne Polymyxa betae- and Polymyxa graminis-transmitted viruses cause extensive crop losses in agriculture and efficient control strategies are missing. We show that GE and Rha both efficiently protect plants against infection with soil-borne viruses in sugar beet and wheat when applied to seeds. Moreover, the antiviral protection effect is independent of the cultivar used. No protection against Polymyxa sp. was observed after seed treatment with the bio-substances at our analysis time points. However, when we applied the bio-substances directly to soil a significant anti-Polymyxa graminis effect was obtained in roots of barley plants grown in the soil as well as in the treated soil. Despite germination can be affected by high concentrations of the substances, a range of antiviral protection conditions with no effect on germination were identified. Seed-treatment with the bio-substances did not negatively affect plant growth and development in virus-containing soil, but was rather beneficial for plant growth. We conclude that seed treatment with GE and Rha may represent an efficient, ecologically friendly, non-toxic, easy to apply and cost efficient biocontrol measure against soil-borne virus infection in plants.

Polysaccharide Peptide Treatment Eliminates Strawberry Viruses and Promotes Strawberry Plant Growth and Rooting in Tissue Culture Media.

Based on our previous finding that polysaccharide peptide (PSP) has substantial antiviral activity, we cultured strawberry plants infected with strawberry mild yellow edge virus (SMYEV) or strawberry vein banding virus (SVBV) in Murashige and Skoog (MS) media supplemented with PSP to test its ability to eliminate these viruses. PSP not only improved the elimination of SMYEV and SVBV but also promoted the growth and rooting of strawberry plants in tissue culture. On the 45th day, the average height of the 'Ningyu' strawberry plants in the 1-mg/ml PSP treatment group was 1.91 cm, whereas that of the plants in the control group was 1.51 cm. After the same time point, the number of new leaves on the tissue culture media supplemented with 1 mg/ml and 500 µg/ml of PSP and without PSP were 4.92, 4.41, and 3.53, respectively. PSP also promoted strawberry rooting and significantly increased both the length and number of roots. In addition, after treatment with the 1-mg/ml PSP treatment in tissue culture for 45 days followed by meristem-shoot-tip culture, the elimination rates of SMYEV and SVBV in regenerated 'Ningyu' strawberry plants ranged from 60 to 100%. This study investigated the use of the antiviral agent PSP for virus elimination. PSP has a low production cost and thus has great application potential for virus elimination in crop plants.

Field application of nanoliposomes delivered quercetin by inhibiting specific hsp70 gene expression against plant virus disease.

BACKGROUND: The annual economic loss caused by plant viruses exceeds 10 billion dollars due to the lack of ideal control measures. Quercetin is a flavonol compound that exerts a control effect on plant virus diseases, but its poor solubility and stability limit the control efficiency. Fortunately, the development of nanopesticides has led to new ideas. RESULTS: In this study, 117 nm quercetin nanoliposomes with excellent stability were prepared from biomaterials, and few surfactants and stabilizers were added to optimize the formula. Nbhsp70er-1 and Nbhsp70c-A were found to be the target genes of quercetin, through abiotic and biotic stress, and the nanoliposomes improved the inhibitory effect at the gene and protein levels by 33.6 and 42%, respectively. Finally, the results of field experiment showed that the control efficiency was 38% higher than that of the conventional quercetin formulation and higher than those of other antiviral agents. CONCLUSION: This research innovatively reports the combination of biological antiviral agents and nanotechnology to control plant virus diseases, and it significantly improved the control efficiency and reduced the use of traditional chemical pesticides.

Autoxidation Products of the Methanolic Extract of the Leaves of Combretum micranthum Exert Antiviral Activity against Tomato Brown Rugose Fruit Virus (ToBRFV).

Tomato brown rugose fruit virus (ToBRFV) is a new damaging plant virus of great interest from both an economical and research point of view. ToBRFV is transmitted by contact, remains infective for months, and to-date, no resistant cultivars have been developed. Due to the relevance of this virus, new effective, sustainable, and operator-safe antiviral agents are needed. Thus, 4-hydroxybenzoic acid was identified as the main product of the alkaline autoxidation at high temperature of the methanolic extract of the leaves of C. micranthum, known for antiviral activity. The autoxidized extract and 4-hydroxybenzoic acid were assayed in in vitro experiments, in combination with a mechanical inoculation test of tomato plants. Catechinic acid, a common product of rearrangement of catechins in hot alkaline solution, was also tested. Degradation of the viral particles, evidenced by the absence of detectable ToBRFV RNA and the loss of virus infectivity, as a possible consequence of disassembly of the virus coat protein (CP), were shown. Homology modeling was then applied to prepare the protein model of ToBRFV CP, and its structure was optimized. Molecular docking simulation showed the interactions of the two compounds, with the amino acid residues responsible for CP-CP interactions. Catechinic acid showed the best binding energy value in comparison with ribavirin, an anti-tobamovirus agent.

Rice black-streaked dwarf virus-encoded P5-1 regulates the ubiquitination activity of SCF E3 ligases and inhibits jasmonate signaling to benefit its infection in rice.

SCF (Skp1/Cullin1/F-box) complexes are key regulators of many cellular processes. Viruses encode specific factors to interfere with or hijack these complexes and ensure their infection in plants. The molecular mechanisms controlling this interference/hijack are currently largely unknown. Here, we present evidence of a novel strategy used by Rice black-streaked dwarf virus (RBSDV) to regulate ubiquitination in rice (Oryza sativa) by interfering in the activity of OsCSN5A. We also show that RBSDV P5-1 specifically affects CSN-mediated deRUBylation of OsCUL1, compromising the integrity of the SCFCOI1 complex. We demonstrate that the expressions of jasmonate (JA) biosynthesis-associated genes are not inhibited, whereas the expressions of JA-responsive genes are down-regulated in transgenic P5-1 plants. More importantly, application of JA to P5-1 transgenic plants did not reduce their susceptibility to RBSDV infection. Our results suggest that P5-1 inhibits the ubiquitination activity of SCF E3 ligases through an interaction with OsCSN5A, and hinders the RUBylation/deRUBylation of CUL1, leading to an inhibition of the JA response pathway and an enhancement of RBSDV infection in rice.

Opuntin B, the antiviral protein isolated from prickly pear (Opuntia ficus-indica (L.) Miller) cladode exhibits ribonuclease activity.

An antiviral protein, designated Opuntin B, was purified from Prickly Pear (Opuntia ficus-indica (L.) Miller) Cladode by heat treatment of the extract, protein precipitation by ammonium sulfate treatment followed by ion-exchange chromatography. Assessment of enzymatic activity of the purified protein showed that it degrades total plant genomic RNA, while causing electrophoretic mobility shifting of Cucumber mosaic virus (CMV) RNAs. However, heat-denatured viral RNA became sensitive to degradation upon treatment with antiviral protein. Opuntin B had no DNase activity on native and heat-denatured apricot genomic DNA, and on PCR-amplified coat protein gene of CMV. Using CMV as prey protein and Opuntin B as bait protein, no interaction was found between the antiviral protein and viral coat protein in far western dot blot analysis.

Identification and Molecular Mechanisms of Key Nucleotides Causing Attenuation in Pathogenicity of Dahlia Isolate of Potato Spindle Tuber Viroid.

While the potato spindle tuber viroid (PSTVd) variant, PSTVd-Dahlia (PSTVd-D or PSTVd-Dwt) induces very mild symptoms in tomato cultivar 'Rutgers', PSTVd-Intermediate (PSTVd-I or PSTVd-Iwt) induces severe symptoms. These two variants differ by nine nucleotides, of which six mutations are located in the terminal left (TL) to the pathogenicity (P) domains. To evaluate the importance of mutations located in the TL to the P domains, ten types of point mutants were created by swapping the nucleotides between the two viroid variants. Bioassay in tomato plants demonstrated that two mutants created on PSTVd-Iwt at positions 42 and 64 resulted in symptom attenuation. Phenotypic and RT-qPCR analysis revealed that mutation at position 42 of PSTVd-Iwt significantly reduced disease severity and accumulation of the viroid, whereas mutation at position 64 showed a significant reduction in stunting when compared to the PSTVd-Iwt infected plant. RT-qPCR analysis on pathogenesis-related protein 1b1 and chalcone synthase genes showed a direct correlation with symptom severity whereas the expansin genes were down-regulated irrespective of the symptom severity. These results indicate that the nucleotides at positions 42 and 64 are in concert with the ones at positions 43, 310, and 311/312, which determines the slower and stable accumulation of PSTVd-D without eliciting excessive host defense responses thus contributing in the attenuation of disease symptom.

Induction of in planta resistance by flagellin (Flg) and elongation factor-TU (EF-Tu) of Bacillus amyloliquefaciens (VB7) against groundnut bud necrosis virus in tomato.

Role of plant growth promoting rhizobacteria (PGPR) in growth promotion and induction of resistance against various plant pathogens have been extensively studied. However, MAMP (Microbe Associated Molecular Pattern) triggered immunity (MTI) against plant viruses are not well exploited. The present study enlightens the role of two MAMP genes including, flagellin (Flg) and elongation factor (EF-Tu) in the induction of plant defense against GBNV infecting tomato. Secondary metabolites of Bacillus amyloliquefaciens (VB7), effectively suppressed GBNV symptom expression up to 84% compared to untreated control in cowpea, the indicator host plant. Agrobacterium tumefaciens EHA105 clones expressing the MAMP genes were drenched in the root zone to assess the induction of resistance against GBNV in tomato. Treatment with A. tumefaciens EHA105 clones containing flagellin (Ag- Ba.Flg) and elongation factor-TU (Ag-Ba.EF-Tu) genes as soil drench and foliar spray, reduced virus titre,0.369 OD and 0.379 OD respectively as compared to control 1.249 OD. The disease severity was reduced up to 15% in Ag-Ba.Flg treated plants compared to 88.25% in inoculated control. Further there was an increased expression of defense associated genes including, MAPKK1, WRKY33BB, NPR1 and PR1.The present investigation clearly indicated the efficiency of MAMP genes in triggering defense mechanism in tomato against GBNV.

Elevated CO2 increases R gene-dependent resistance of Medicago truncatula against the pea aphid by up-regulating a heat shock gene.

Resistance against pathogens and herbivorous insects in many plant results from the expression of resistance (R) genes. Few reports, however, have considered the effects of elevated CO2 on R gene-based resistance in plants. The current study determined the responses of two near isogenic Medicago truncatula genotypes (Jester has an R gene and A17 does not) to the pea aphid and elevated CO2 in open-top chambers in the field. Aphid abundance, mean relative growth rate and feeding efficiency were increased by elevated CO2 on A17 plants but were reduced on Jester plants. According to proteomic and gene expression data, elevated CO2 enhanced pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) but decreased the effector-triggered immunity (ETI) in aphid-infested A17 plants. For aphid-infested Jester plants, by contrast, elevated CO2 enhanced the ETI-related heat shock protein (HSP) 90 and its co-chaperones, the jasmonic acid (JA) signaling pathway, and ubiquitin-mediated proteolysis. In a loss-of-function experiment, silencing of the HSP90 gene in Jester plants impaired the JA signaling pathway and ubiquitin-mediated proteolysis against the aphid under ambient CO2 , and negated the increased resistance against the aphid under elevated CO2 . Our results suggest that increases in expression of HSP90 are responsible for the enhanced resistance against the aphid under elevated CO2 .

Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection.

Tyrosinase inhibitory components from Aloe vera and their antiviral activity.

A new compound, 9-dihydroxyl-2'-O-(Z)-cinnamoyl-7-methoxy-aloesin (1), and eight known compounds (2-9) were isolated from Aloe vera. Their structures were elucidated using 1D/2D nuclear magnetic resonance and mass spectra. Compound 9 exhibited reversible competitive inhibitory activity against the enzyme tyrosinase, with an IC50 value of 9.8 ± 0.9 µM. A molecular simulation revealed that compound 9 interacts via hydrogen bonding with residues His244, Thr261, and Val283 of tyrosinase. Additionally, compounds 3 and 7 were shown by half-leaf assays to exhibit inhibitory activity towards Pepper mild mottle virus.

Advances and prospects in biogenic substances against plant virus: A review.

Plant virus diseases, known as 'plant cancer', are the second largest plant diseases after plant fungal diseases, which have caused great damage to agricultural industry. Since now, the most direct and effective method for controlling viruses is chemotherapeutics, except for screening of anti-disease species. As the occurrence and harm of plant diseases intensify, production and consumption of pesticides have increased year by year, and greatly contributed to the fertility of agriculture, but also brought a series of problems, such as the increase of drug resistance of plant pathogens and the excessive pesticide residues. In recent years, biopesticide, as characterized by environmentally safe due to low residual, safe to non-target organism due to better specificity and not as susceptible to produce drug resistance due to diverse work ways, has gained more attention than ever before and exhibited great development potential. Now much progress has been made about researches on new biogenic anti-plant-virus substances. The types of active components include proteins, polysaccharides and small molecules (alkaloids, flavonoids, phenols, essential oils) from plants, proteins and polysaccharides from microorganisms, polysaccharides from algae and oligochitosan from animals. This study summarized the research advance of biogenic anti-plant-virus substances in recent years and put forward their further development in the future.

Double-stranded RNAs induce a pattern-triggered immune signaling pathway in plants.

Pattern-triggered immunity (PTI) is a plant defense response that relies on the perception of conserved microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs, respectively). Recently, it has been recognized that PTI restricts virus infection in plants; however, the nature of the viral or infection-induced PTI elicitors and the underlying signaling pathways are still unknown. As double-stranded RNAs (dsRNAs) are conserved molecular patterns associated with virus replication, we applied dsRNAs or synthetic dsRNA analogs to Arabidopsis thaliana and investigated PTI responses. We show that in vitro-generated dsRNAs, dsRNAs purified from virus-infected plants and the dsRNA analog polyinosinic-polycytidylic acid (poly(I:C)) induce typical PTI responses dependent on the co-receptor SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1 (SERK1), but independent of dicer-like (DCL) proteins in Arabidopsis. Moreover, dsRNA treatment of Arabidopsis induces SERK1-dependent antiviral resistance. Screening of Arabidopsis wild accessions demonstrates natural variability in dsRNA sensitivity. Our findings suggest that dsRNAs represent genuine PAMPs in plants, which induce a signaling cascade involving SERK1 and a specific dsRNA receptor. The dependence of dsRNA-mediated PTI on SERK1, but not on DCLs, implies that dsRNA-mediated PTI involves membrane-associated processes and operates independently of RNA silencing. dsRNA sensitivity may represent a useful trait to increase antiviral resistance in cultivated plants.

Evaluation of disinfectants to prevent mechanical transmission of viruses and a viroid in greenhouse tomato production.

BACKGROUND: In recent years, a number of serious disease outbreaks caused by viruses and viroids on greenhouse tomatoes in North America have resulted in significant economic losses to growers. The objectives of this study were to evaluate the effectiveness of commercial disinfectants against mechanical transmission of these pathogens, and to select disinfectants with broad spectrum reactivity to control general virus and viroid diseases in greenhouse tomato production. METHODS: A total of 16 disinfectants were evaluated against Pepino mosaic virus (PepMV), Potato spindle tuber viroid (PSTVd), Tomato mosaic virus (ToMV), and Tobacco mosaic virus (TMV). The efficacy of each disinfectant to deactivate the pathogen's infectivity was evaluated in replicate experiments from at least three independent experiments. Any infectivity that remained in the treated solutions was assessed through bioassays on susceptible tomato plants through mechanical inoculation using inocula that had been exposed with the individual disinfectant for three short time periods (0-10 sec, 30 sec and 60 sec). A positive infection on the inoculated plant was determined through symptom observation and confirmed with enzyme-linked immunosorbent assay (PepMV, ToMV, and TMV) and real-time reverse transcription-PCR (PSTVd). Experimental data were analyzed using Logistic regression and the Bayesian methodology. RESULTS: Statistical analyses using logistic regression and the Bayesian methodology indicated that two disinfectants (2% Virkon S and 10% Clorox regular bleach) were the most effective to prevent transmission of PepMV, PSTVd, ToMV, and TMV from mechanical inoculation. Lysol all-purpose cleaner (50%) and nonfat dry milk (20%) were also effective against ToMV and TMV, but with only partial effects for PepMV and PSTVd. CONCLUSION: With the broad spectrum efficacy against three common viruses and a viroid, several disinfectants, including 2% Virkon S, 10% Clorox regular bleach and 20% nonfat dry milk, are recommend to greenhouse facilities for consideration to prevent general virus and viroid infection on tomato plants.

Antiviral activity of mycophenolic acid derivatives in plants.

KEYWORDS: antiviral agents; chemotherapy; polyamidoamine; multivalency.

The acyclic nucleoside phosphonates (ANPs): Antonín Holý's legacy.

The name of Antonín Holý has become synonymous for the era of acyclic nucleoside phosphonates (ANPs), which started with (S)-HPMPA as the prototype and (S)-HPMPC (cidofovir) as the first marketed compound. It has now evolved to a number of compounds clinically used in the treatment of HIV and hepatitis B virus infections, either as such [tenofovir disoproxil fumarate (TDF, Viread®)] or in combination [Truvada®, Atripla®, Complera®, Stribild®]. Truvada has also been approved for the prevention of HIV infections. Forthcoming is a new formulation of tenofovir (TAF: tenofovir alafenamide). Also forthcoming are several "quad" drug combinations containing either TDF or TAF. Other ANPs, based on either an alkoxy side chain or 5-azacytosine heterocycle seem highly promising and worth further pursuing.

Comparison of early transcriptome responses to copper and cadmium in rice roots.

The phytotoxic effects of copper (Cu) and cadmium (Cd) on plant growth are well documented. However, Cu and Cd toxicity targets and the cellular systems contributing to acquisition of tolerance are not fully understood at the molecular level. We aimed to identify genes and pathways that discriminate the actions of Cu and Cd in rice roots (Oryza sativa L. cv. TN67). The transcripts of 1,450 and 1,172 genes were regulated after Cu and Cd treatments, respectively. We identified 882 genes specifically respond to Cu treatment, and 604 unique genes as Cd-responsive by comparison of expression profiles of these two regulated gene groups. Gene ontology analysis for 538 genes involved in primary metabolism, oxidation reduction and response to stimulus was changed in response to both metals. In the individual aspect, Cu specifically altered levels of genes involved in vesicle trafficking transport, fatty acid metabolism and cellular component biogenesis. Cd-regulated genes related to unfolded protein binding and sulfate assimilation. To further characterize the functions of vesicle trafficking transport under Cu stress, interference of excytosis in root tissues was conducted by inhibitors and silencing of Exo70 genes. It was demonstrated that vesicle-trafficking is required for mediation of Cu-induced reactive oxygen species (ROS) production in root tissues. These results may provide new insights into understanding the molecular basis of the early metal stress response in plants.

Alpha-momorcharin, a RIP produced by bitter melon, enhances defense response in tobacco plants against diverse plant viruses and shows antifungal activity in vitro.

Alpha-momorcharin (α-MMC) is type-1 ribosome inactivating proteins (RIPs) with molecular weight of 29 kDa and has lots of biological activity. Our recent study indicated that the α-MMC purified from seeds of Momordica charantia exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated with 0.5 mg/mL α-MMC 3 days before inoculation with various viruses showed less-severe symptom and less reactive oxygen species (ROS) accumulation compared to that inoculated with viruses only. Quantitative real-time PCR analysis revealed that the replication levels of viruses were lower in the plants treated with the α-MMC than control plants at 15 days post inoculation. Moreover, the coat protein expression of viruses was almost completely inhibited in plants which were treated with the α-MMC compared with control plants. Furthermore, the SA-responsive defense-related genes including non-expressor of pathogenesis-related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) were increased after the α-MMC treatment. In addition, the α-MMC (500 µg/mL) revealed remarkable antifungal effect against phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with their MIC values ranging from 100 to 500 µg/mL. The α-MMC had also a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of Sclerotinia sclerotiorum. The α-MMC showed a remarkable antiviral and antifungal effect and hence could possibly be exploited in crop protection for controlling certain important plant diseases.

Elevated CO2 spurs reciprocal positive effects between a plant virus and an arbuscular mycorrhizal fungus.

Plants form ubiquitous associations with diverse microbes. These interactions range from parasitism to mutualism, depending partly on resource supplies that are being altered by global change. While many studies have considered the separate effects of pathogens and mutualists on their hosts, few studies have investigated interactions among microbial mutualists and pathogens in the context of global change. Using two wild grass species as model hosts, we grew individual plants under ambient or elevated CO(2), and ambient or increased soil phosphorus (P) supply. Additionally, individuals were grown with or without arbuscular mycorrhizal inoculum, and after 2 wk, plants were inoculated or mock-inoculated with a phloem-restricted virus. Under elevated CO(2), mycorrhizal association increased the titer of virus infections, and virus infection reciprocally increased the colonization of roots by mycorrhizal fungi. Additionally, virus infection decreased plant allocation to root biomass, increased leaf P, and modulated effects of CO(2) and P addition on mycorrhizal root colonization. These results indicate that plant mutualists and pathogens can alter each other's success, and predict that these interactions will respond to increased resource availability and elevated CO(2). Together, our findings highlight the importance of interactions among multiple microorganisms for plant performance under global change.

Probing the Nucleic Acid Flexibility to Disarm the Viral Counter-Defense Machinery: Design and Characterization of Potent p19 Inhibitors.

Plant viruses are highly destructive and significant contributors to several global pandemics and epidemics in plants. A viral disease outbreak in plants can cause a scarcity of food supply and is a severe concern to humanity. The siRNA (small interfering RNA)-mediated RNA-induced silencing complex (RISC) formation is a primary defense mechanism in plants against viruses, where the RISC binds and degrades viral mRNAs. As a counter-defense, many viruses encode RNA-silencing suppressor proteins (e.g., the p19 protein from the Tombusviridae family) for viral proliferation in plants. The functional form of p19 (homodimer) binds to plant siRNA with high affinities, thereby interrupting the RISC formation and thus preventing the viral mRNA silencing in plants. By altering the RISC formation, the p19 protein helps the virus invasion in the plant and ultimately stunts host growth. In this study, we designed several modified siRNA-based molecules for p19 inhibition. The viral p19 protein is known to interact predominantly through H-bonds with 2'-OH and phosphates of the plant siRNA. We utilized this information and in silico-designed flexible substituents of siRNA, where we removed the C2'-C3' bond in each nucleotide unit. We performed all-atom explicit-solvent molecular dynamics simulations (400 ns, 3 replicates each) for control/modified siRNA─p19 complexes (8 in total) followed by energetic estimations. Strikingly, in a few modified complexes, the siRNA not only retained the double-helical structural integrity but also displayed remarkably enhanced p19 binding compared to the control siRNA; hence, we consider it important to perform biological and chemical in vitro and in vivo studies on proposed flexible nucleic acids as p19 inhibitors for crop protection.