ChemFREE: a one-stop comprehensive platform for ecological and environmental risk evaluation of chemicals in one health world.

Addressing health and safety crises stemming from various environmental and ecological issues is a core focus of One Health (OH), which aims to balance and optimize the health of humans, animals, and the environment. While many chemicals contribute significantly to our quality of life when properly used, others pose environmental and ecological health risks. Recently, assessing the ecological and environmental risks associated with chemicals has gained increasing significance in the OH world. In silico models may address time-consuming and costly challenges, and fill gaps in situations where no experimental data is available. However, despite their significant contributions, these assessment models are not web-integrated, leading to user inconvenience. In this study, we developed a one-stop comprehensive web platform for freely evaluating the eco-environmental risk of chemicals, named ChemFREE (Chemical Formula Risk Evaluation of Eco-environment, available in http://chemfree.agroda.cn/chemfree/). Inputting SMILES string of chemicals, users will obtain the assessment outputs of ecological and environmental risk, etc. A performance evaluation of 2935 external chemicals revealed that most classification models achieved an accuracy rate above 0.816. Additionally, the $Q_{F1}^2$ metric for regression models ranges from 0.618 to 0.898. Therefore, it will facilitate the eco-environmental risk evaluation of chemicals in the OH world.

Bioinformatics toolbox for exploring target mutation-induced drug resistance.

Drug resistance is increasingly among the main issues affecting human health and threatening agriculture and food security. In particular, developing approaches to overcome target mutation-induced drug resistance has long been an essential part of biological research. During the past decade, many bioinformatics tools have been developed to explore this type of drug resistance, and they have become popular for elucidating drug resistance mechanisms in a low cost, fast and effective way. However, these resources are scattered and underutilized, and their strengths and limitations have not been systematically analyzed and compared. Here, we systematically surveyed 59 freely available bioinformatics tools for exploring target mutation-induced drug resistance. We analyzed and summarized these resources based on their functionality, data volume, data source, operating principle, performance, etc. And we concisely discussed the strengths, limitations and application examples of these tools. Specifically, we tested some predictive tools and offered some thoughts from the clinician's perspective. Hopefully, this work will provide a useful toolbox for researchers working in the biomedical, pesticide, bioinformatics and pharmaceutical engineering fields, and a good platform for non-specialists to quickly understand drug resistance prediction.

In Addition to Damaging the Plasma Membrane, Phenolic Monoterpenoid Carvacrol Can Bind to the Minor Groove of DNA of Phytopathogenic Fungi to Potentially Control Tea Leaf Spot Caused by Lasiodiplodia theobromae.

Carvacrol expresses a wide range of biological activities, but the studies of its mechanisms focused on bacteria, mainly involving the destruction of the plasma membrane. In this study, carvacrol exhibited strong activities against several phytopathogenic fungi and demonstrated a novel antifungal mechanism against Lasiodiplodia theobromae. RNA sequencing indicated that many genes of L. theobromae hyphae were predominately induced by carvacrol, particularly those involved in replication and transcription. Hyperchromic, hypsochromic, and bathochromic effects in the UV-visible absorption spectrum were observed following titration of calf thymus DNA (ctDNA) and carvacrol, which indicated the formation of a DNA-carvacrol complex. Circular dichroism (CD) spectroscopy indicated that the response of DNA to carvacrol was similar to that of 4',6-diamidino-2-phenylindole (DAPI) but different from that of ethidium bromide (EB), implying the ionic bonds between carvacrol and ctDNA. Fluorescence spectrum (FS) analysis indicated that carvacrol quenched the fluorescence of double-stranded DNA (dsDNA) more than single-stranded DNA, indicating that carvacrol mainly bound to dsDNA. A displacement assay showed that carvacrol reduced the fluorescence intensity of the DNA-DAPI complex through competition with DAPI, but this did not occur for DNA-EB. The FS assay revealed that carvacrol bound to the AAA sequence on the minor groove of ds-oligonucleotides. The hydroxyl of carvacrol was verified to bind to ctDNA through a comparative test in which structural analogs of carvacrol, including thymol and 4-ethyl-1,2-dimethyl, were analyzed. The current study indicated carvacrol can destruct plasma membranes and bind to the minor groove of DNA, inhibiting fungal proliferation by disturbing the stability of dsDNA.

Design, synthesis and bactericidal activity of novel coumarin derivatives containing pyridinium salts.

Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.

Web repositories of natural agents promote pests and pathogenic microbes management.

The grand challenge to meet the increasing demands for food by a rapidly growing global population requires protecting crops from pests. Natural active substances play a significant role in the sustainable pests and pathogenic microbes management. In recent years, natural products- (NPs), antimicrobial peptides- (AMPs), medicinal plant- and plant essential oils (EOs)-related online resources have greatly facilitated the development of pests and pathogenic microbes control agents in an efficient and economical manner. However, a comprehensive comparison, analysis and summary of these existing web resources are still lacking. Here, we surveyed these databases of NPs, AMPs, medicinal plants and plant EOs with insecticidal, antibacterial, antiviral and antifungal activity, and we compared their functionality, data volume, data sources and applicability. We comprehensively discussed the limitation of these web resources. This study provides a toolbox for bench scientists working in the pesticide, botany, biomedical and pharmaceutical engineering fields. The aim of the review is to hope that these web resources will facilitate the discovery and development of potential active ingredients of pests and pathogenic microbes control agents.

Integrated Transcriptome and Proteome Analysis Reveals that the Antimicrobial Griseofulvin Targets Didymella segeticola Beta-Tubulin to Control Tea Leaf Spot.

Because effective control measures are lacking, tea leaf spot caused by Didymella segeticola results in huge tea (Camellia sinensis) production losses on tea plantations in Guizhou Province, southwestern China. Screening for natural antimicrobial agents with higher control effects against this pathogen and studying their modes of action may contribute to disease management. Here, Penicillium griseofulvum-derived antimicrobial griseofulvin (GSF) can inhibit the hyphal growth of D. segeticola strain GZSQ-4, with a half-maximal effective concentration of 0.37 µg/ml in vitro and a higher curative efficacy at a lower dose of 25 µg/ml for detached tea twigs. GSF induces deformed and slightly curly hyphae with enlarged ends, with protoplasts agglutinated in the hyphae, and higher numbers of hyphal protuberances. GSF alters hyphal morphology and the subcellular structure's order. The integrated transcriptome and proteome data revealed that the transport of materials in cells, cellular movement, and mitosis were modulated by GSF. Molecular docking indicated that beta-tubulin was the most potent target of GSF, with a binding free energy of -13.59 kcal/mol, and microscale thermophoresis indicated that the dissociation constant (Kd) value of GSF binding to beta-tubulin 1, compared with beta-tubulin 2, was significantly lower. Thus, GSF potentially targets beta-tubulin 1 to disturb the chromosomal separation and fungal mitosis, thereby inhibiting hyphal growth.

Ubiquitin-Like protein 5 interacts with the silencing suppressor p3 of rice stripe virus and mediates its degradation through the 26S proteasome pathway.

Ubiquitin like protein 5 (UBL5) interacts with other proteins to regulate their function but differs from ubiquitin and other UBLs because it does not form covalent conjugates. Ubiquitin and most UBLs mediate the degradation of target proteins through the 26S proteasome but it is not known if UBL5 can also do that. Here we found that the UBL5s of rice and Nicotiana benthamiana interacted with rice stripe virus (RSV) p3 protein. Silencing of NbUBL5s in N. benthamiana facilitated RSV infection, while UBL5 overexpression conferred resistance to RSV in both N. benthamiana and rice. Further analysis showed that NbUBL5.1 impaired the function of p3 as a suppressor of silencing by degrading it through the 26S proteasome. NbUBL5.1 and OsUBL5 interacted with RPN10 and RPN13, the receptors of ubiquitin in the 26S proteasome. Furthermore, silencing of NbRPN10 or NbRPN13 compromised the degradation of p3 mediated by NbUBL5.1. Together, the results suggest that UBL5 mediates the degradation of RSV p3 protein through the 26S proteasome, a previously unreported plant defense strategy against RSV infection.

Rapid and sensitive detection of ammonia in water by a long period fiber grating sensor coated with sol-gel silica.

A sensitive ammonia sensor based on long-period fiber grating (LPFG) is designed and manufactured for the detection of ammonia concentration in water. Femtosecond laser direct writing technology is used to write LPFGs on standard single-mode silica fiber. A thin layer doped with basic dyes is coated on the optical fiber for sensing by using the sol-gel method. The thicknesses of sol-gel layers, which play a key role in the sensitivity of the LPFG sensor, were carefully studied. Experimental results show that LPFG with a functional layer of ∼340 nm has the best sensing performance, and the detection limit is 0.08 ppm. The response time of the sensor is less than one minute, and the sensor has good repeatability with a short recovery time. Compared with other organic molecules and ions in water, the proposed LPFG sensor has not only good reusability, but also selectivity for the detection of ammonia.

Multi-Omics Analysis Reveals that the Antimicrobial Kasugamycin Potential Targets Nitrate Reductase in Didymella segeticola to Achieve Control of Tea Leaf Spot.

Because of the lack of effective disease management measures, tea leaf spot-caused by the fungal phytopathogen Didymella segeticola (syn. Phoma segeticola)-is an important foliar disease. The important and widely used agricultural antimicrobial kasugamycin (Ksg), produced by the Gram-positive bacterium Streptomyces kasugaensis, effects high levels of control against crop diseases. The results of this study indicated that Ksg could inhibit the growth of D. segeticola hyphae in vitro with a half-maximal effective concentration (EC50) of 141.18 µg ml-1. Meanwhile, the curative effect in vivo on the pathogen in detached tea leaves also demonstrated that Ksg induced some morphological changes in organelles, septa, and cell walls as observed by optical microscopy and by scanning and transmission electron microscopy. This may indicate that Ksg disturbs biosynthesis of key metabolites, inhibiting hyphal growth. Integrated transcriptomic, proteomic, and bioinformatic analyses revealed that differentially expressed genes or differentially expressed proteins in D. segeticola hyphae in response to Ksg exposure were involved with metabolic processes and biosynthesis of secondary metabolites. Molecular docking studies indicated that Ksg may target nitrate reductase (NR), and microscale thermophoresis assay showed greater affinity with NR, potentially disturbing nitrogen assimilation and subsequent metabolism. The results indicated that Ksg inhibits the pathogen of tea leaf spot, D. segeticola, possibly by binding to NR, disturbing fungal metabolism, and inducing subsequent changes in hyphal growth and development.

A Novel Sulfone Derivative Controls Lasiodiplodia theobromae in Tea Leaf Spot by Reducing the Ergosterol Content.

Diseases caused by fungi can affect the quality and yield of the leaves of tea [Camellia sinensis (L.) Kuntze]. At present, the availability of highly effective and safe fungicides for controlling tea plants remains limited. The objectives of this study were to identify novel compounds with antifungal activities and to determine their molecular mechanisms. A series of sulfone compounds containing 1,3,4-oxadiazole were evaluated in China for their antifungal activities against several pathogens causing foliar diseases and high production losses. Transcriptomics and bioinformatics were used to analyze the differentially expressed genes of Lasiodiplodia theobromae treated with a representative compound, jiahuangxianjunzuo (JHXJZ). Moreover, the effects of JHXJZ on ergosterol content, membrane permeability, cell structure, and seven key genes involved in the ergosterol biosynthetic pathway were investigated. JHXJZ had a strong antifungal activity against L. theobromae in vitro, with an effective concentration giving 50% inhibition of 3.54 ± 0.55 µg/ml, and its curative efficacies on detached tea leaves reached 41.78% at 100 µg/ml. JHXJZ upregulated 899 genes (P < 0.05) and downregulated 1,185 genes (P < 0.05) in L. theobromae. These genes were found to be associated with carbohydrate metabolic processes, which are closely related to steroid biosynthesis in the Kyoto Encyclopedia of Genes and Genomes pathways. Because JHXJZ regulates the key genes of sterol biosynthesis, it decreased the ergosterol content, increased cell-membrane permeability, changed the cellular structure, enhanced the roughness of the surface of the hyphae, and resulted in degradation of the hyphal nuclei and necrosis of the hyphal cytoplasm. Our study demonstrates that JHXJZ is a fungicide with a novel mechanism of action that differs from that of triazole fungicides. JHXJZ has potential for applications in controlling tea plant diseases.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Spectral fitting method for obtaining the refractive index and thickness of chalcogenide films.

Spectral fitting method (SFM) was proposed to obtain the refractive index (RI) and thickness of chalcogenide films based on transmission spectra. It extended the Swanepoel method to the films on the order of hundreds of nanometers in thickness. The RI and thickness of the films can be obtained quickly and accurately by using the SFM based on the transmission spectrum with only one peak and valley. The method's reliability theoretically was evaluated by simulation analysis. The results showed that the accuracy of the RI and thickness was better than 0.2% by using the SFM regardless of thin or thick film. Finally, the RI and thickness of the new ultralow loss reversible phase-change material Sb2Se3 films were obtained experimentally by the SFM. This work should provide a useful guideline for obtaining the RI and thickness of the transparent optical films.

Discovery of novel chromone derivatives containing a sulfonamide moiety as potential anti-TSWV agents.

A number of chromone derivatives containing sulfonamide structure were designed and synthesized. Firstly, the target compounds were evaluated for anti-TSWV activities in vivo by the half-leaf method. We found that most of the compounds had good anti-TSWV activities. Among them, compound 12B had excellent anti-TSWV inactivating activity with an EC50 of 80.5 µg/mL, which was significantly better than xiangcaoliusuobingmi (765.7 µg/mL). Secondly, TSWV nucleocapsid protein (N) was expressed and purified, and the affinity between the compounds and TSWV N was tested by microscale thermophoresis (MST). Compound 12B had a good affinity for TSWV N with a Kd value of 5.02 µM, which was superior to xiangcaoliusuobingmi (29.83 µM). Finally, in order to study the mode of interaction between the compound 12B and TSWV N, we carried out molecular docking. The results indicated that compound 12B might inactivate the virus by destroying the TSWV N oligomer structure. These results lay a solid foundation for the further discovery of chromone derivatives containing sulfonamide structure with high anti-TSWV activities.

Integration of Transcriptomic and Proteomic Data Reveals the Possible Action Mechanism of the Antimicrobial Zhongshengmycin Against Didymella segeticola, the Causal Agent of Tea Leaf Spot.

Tea leaf spot, caused by the fungal phytopathogen Didymella segeticola, is an important foliar disease that can cause huge losses in the production and quality of tea, and there are no effective management measures to control the disease. This study screened a natural antimicrobial chemical for its activity against D. segeticola and studied its mode of action. Antifungal activity of the Streptomyces-derived antimicrobial zhongshengmycin (ZSM) against D. segeticola strain GZSQ-4 was assayed in vitro via the mycelial growth rate method. Optical microscopy and scanning and transmission electron microscopy were used to observe the morphological effects on hyphae treated with ZSM, with these studies complemented by transcriptomic, proteomic, and bioinformatic studies to identify the differentially expressed genes or differentially expressed proteins in hyphae treated with ZSM. Correlation analysis of transcriptomic and proteomic data were used to reveal the mode of action. The results indicated that ZSM could inhibit the growth of hyphae in vitro with a half-maximal effective concentration of 5.9 µg/ml, inducing some morphological changes in organelles, septa, and extracellular polysaccharides, targeting ribosomes to disturb translation, affecting the biosynthesis of some hyphal proteins at the messenger RNA and protein levels, and revealing correlations between findings from transcriptomes and proteomes.

Novel vanillin derivatives containing a 1,3,4-thiadiazole moiety as potential antibacterial agents.

In this study, thirty-four novel vanillin derivatives containing a 1,3,4-thiadiazole structure were obtained and their antibacterial activities were evaluated. The results indicate that most of the title compounds displayed inhibitory effects on Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc). Among them, compound 29 exhibited excellent antibacterial activities against Xoo and Xoc in vitro, with the EC50 values of 3.14 and 8.83 µg/mL, respectively, much superior to thiodiazole copper (87.03 and 108.99 µg/mL) and bismerthiazol (67.64 and 79.26 µg/mL). Under greenhouse condition, the protective efficiency of compound 29 against rice bacterial leaf blight was 49.34%, and curative efficiency was 40.96%. In addition, compound 29 can reduce the exopolysaccharides production of Xoo, increase the permeability of cell membrane and damage cell membrane.

Design, synthesis and anti-TMV activities of novel chromone derivatives containing dithioacetal moiety.

Thirty-five novel chromone derivatives containing dithioacetal moiety were designed, synthesized, and their anti-TMV activities were evaluated through half-leaf method. The results showed compound c23 illustrates highly curative, protective and inactivating activities against TMV at 500 mg/L, with the values of 68.8%, 58.8%, 86.0% respectively, which were superior to that of Ribavirin (42.3%, 49.8%, 68.4%, respectively) and similar to that of Ningnanmycin (59.4%, 52.4%, 88.4%, respectively). The EC50 value of inactivating activities of compound c23 is 9.3 mg/L, which was better than that of Ribavirin (135.2 mg/L), and equivalent to that of Ningnanmycin (8.8 mg/L). Furthermore, compound c23 can destroy the integrity of TMV-CP, resulting in reduced infectivity of TMV. Meanwhile, compound c23 can combine with TMV protein coat and hydrolyze TMV protein coat to impact the process of self-assembling of TMV, with the association constant (Kd) 4.5 mg/L. This finding suggests that chromone derivatives containing dithioacetal moiety can be used as new antiviral agent.

Novel 1,3,4-oxadiazole thioether derivatives containing flexible-chain moiety: Design, synthesis, nematocidal activities, and pesticide-likeness analysis.

Seventy-two novel 1,3,4-oxadiazole thioether derivatives containing different flexible-chain moieties were designed and synthesized. The nematicidal activities of all the title compounds were evaluated, and some compounds showed excellent nematicidal activities against citrus nematodes. The compounds 15, 16, 18, 27, 41, 42, 44, 53, and 71 had the mortality to citrus nematodes of 92.5, 93.7, 90.3, 91.5, 92.6, 92.8, 93.5, 91.3, and 91.0% at the concentration of 100 mg/L, which were better than the control agent of avermectin (85.9%). After the test concentration was reduced to 50 mg/L, the nematicidal activities of the compounds 16, 42, 44, 53, and 71 were still superior to avermectin (65.1%), with the mortality of 72.3, 71.3, 70.6, 71.1, and 73.9%, respectively. The LC50 values of the compounds 16, 42, 44, 53, and 71 were 16.3, 18.8, 20.8, 17.5, and 14.7 mg/L, which were better than the commercial positive control agent of avermectin (24.8 mg/L). Meanwhile, the qualitative and quantitative analysis of the pesticide-likeness shows that compound 71 exhibits the potential insecticide-likeness. This work indicates that novel 1,3,4-oxadiazole thioether derivatives containing flexible-chains deserve further research as potential nematicides to protect citrus crops in the future.

α-Haloacetophenone and analogues as potential antibacterial agents and nematicides.

A series of α-haloacetophenones and analogues were synthesized. The bioassays show that some target compounds have good antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Meloidogyne incognita (M. incognita). Especially, the compound 24 has good in vitro and in vivo antibacterial activities against Xoo, the EC50 value, curative and protection activities are 0.09 mg/L, 48.9%, and 52.3%, respectively, which are better than the thiodiazole copper and bismerthiazol. Meanwhile, the compound 24 has good in vitro antibacterial activity against Xac, and has an EC50 value of 1.6 mg/L. Moreover, the compound 19 exhibits good nematicidal activity M. incognita, with the LC50 value of 1.0 mg/L, which is better than the positive control avermectin. In addition, the compound 24 can inhibit the formation of extracellular polysaccharide and biofilm of Xoo, and change the permeability of cell membrane. α-haloacetophenone and analogues have the advantages of simple structure, high efficiency, broad spectrum of biological activity, and can be used as antibacterial agents and nematicides or lead compounds in the future.

First report about the screening, characterization, and fosmid library construction of Xanthomonas oryzae pv. oryzae strain with resistance to Fubianezuofeng.

Bacterial blight (BB), which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is a common bacterial disease that seriously harms rice production in major rice-growing areas worldwide. Fubianezuofeng (FBEZF), a sulfone bactericide that contains an oxadiazole moiety, exerts good control effect on BB. In this study, FBEZF-resistant strains of Xoo were screened for the first time in the laboratory to evaluate the risk of Xoo developing resistance to FBEZF. Three strains with moderate resistance to FBEZF, were obtained and named as F1, F2, and F3, which have resistance factors (RF) of 14.69, 15.72, and 11.12, respectively. FBEZF lacked positive cross-resistance to bismerthiazol, thiodiazole copper, zhongshengmycin and phenazino-1-carboxylic acid. The growth rates of the resistant strains F1 and F2 were similar to those of the wild-type strain in nutrient broth medium, but differed in nutrient agar medium. The extracellular polysaccharide production and pathogenicity of F1, F2, and F3 were reduced relative to those of the wild-type strain. A fosmid library containing 2304 transformants was constructed based on the genome of F2, and transformants 2193 and 2202 exhibited FBEZF resistance. The results are helpful for further study on the molecular mechanism of resistance to FBEZF in Xoo.

Design and synthesis of novel 1,3,4-oxadiazole sulfone compounds containing 3,4-dichloroisothiazolylamide moiety and evaluation of rice bacterial activity.

In this study, thirty 1,3,4-oxadiazole sulfone derivatives containing 3,4-dichloroisothiazolamide moiety were designed and synthesized, and their antibacterial activities were evaluated. Bioassay results showed that some compounds exhibited excellent antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) in vitro and in vivo. Notably, the EC50 values of compounds 2 and 3 against Xoo were 0.79 and 0.85 µg/mL, respectively, which were superior to those of the control agents isotianil, bismerthiazol, and thiodiazole copper. In addition, in vivo antibacterial activities revealed that the compound 2 at 50 µg/mL possessed protective and curative activities of 43.99% and 41.06% against Xoo, respectively, which were better than positive controls. Furthermore, the preliminary mechanism study disclosed that compound 2 exhibited effective antibacterial activity against Xoo by inhibiting the formation of extracellular polysaccharides from Xoo, increasing cell permeability, and changing the shape of cells. This study suggested that 1,3,4-oxadiazole sulfone derivatives containing 3,4-dichloroisothiazolamide moiety displayed excellent antibacterial activity and could be further explored and developed as commercial pesticides.

Naturally potential antiviral agent polysaccharide from Dendrobium nobile Lindl.

A polysaccharide DNPE6(11) was purified from Dendrobium nobile Lindl. (D. nobile Lindl.). Its structural characteristic, antiviral activity, and preliminary mechanism were studied. The structural characteristic analysis indicated that DNPE6(11) was a novel homogenous heteropolysaccharide from D. nobile Lindl. Bioactivity assays indicated that DNPE6(11) possessed outstanding curative and inactivating activities against cucumber mosaic virus, which were superior to chitosan oligosaccharide and lentinan. Additionally, DNPE6(11) exhibited notable protective activity against potato virus Y, which was better than Ningnanmycin. Furthermore, the preliminary mechanism study found that DNPE6(11) cannot accumulate salicylic acid to induce systemic acquired resistance, but had a strong binding capacity for cucumber mosaic virus coat protein. Therefore, DNPE6(11) could be considered as a promising antiviral agent to study in the future.