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[Objective] Plasmodium vivax predominantly infects many people in numerous tropical areas, including Southeast Asia, the Western Pacific, the Americas, and the Eastern Mediterranean. The uniqueness of forming dormant stages can lead to relapse in vivax malaria upon further infection. This study used molecular docking and dynamic simulation to predict potential bioactive compounds from the Zingiberaceae plant family as inhibitors by targeting Plasmodium vivax Duffy Binding Protein (PvDBP). PvDBP-DARC molecular interaction is required to mediate the merozoite invasion process into red blood cells. Inhibiting this process can possibly control parasite growth and development. [Methodology] Molecular docking screening was conducted by using 138 natural compounds from the Zingiberaceae plant family targeting Plasmodium vivax Duffy binding protein (PvDBP). The top two compounds with the lowest binding energy were selected to be analyzed by pharmacokinetics prediction and molecular dynamic (MD) simulation. [Results] Molecular docking screening resulted in the top two compounds with the lowest binding energy value, including 5,7-dihydroxyflavanone (-9.3 kcal/mol) and pinostrobin (-9.2 kcal/mol). These compounds are predicted to have stronger interaction than chloroquine as a control. Furthermore, the potential compounds also interact with DARC binding site residues and maintain them during the molecular dynamic simulation process. Otherwise, chloroquine as a control cannot retain 75% binding residues towards PvDBP. A molecular dynamic study revealed that all three complexes have relatively similar stability. [Conclusions] We predicted that the two bioactive compounds (5,7-dihydroxyflavanone and pinostrobin) have the potential as merozoite invasion inhibitors.

Abstract The oncoprotein E6, a pivotal player in HPV-16-induced cancer, has long been the focus of extensive research. Building upon our previous study, we identified asarinin and thiazolo[3,2-a] benzimidazole-3(2H)-one-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo) as potential potent anti-HPV-16 E6 oncoprotein agents. Utilizing the UniProt-derived E6 sequence, we employed I-TASSER to model the protein's three-dimensional structure. Subsequent molecular docking via AutoDock Vina, coupled with a 1,000 ps dynamic analysis under physiological parameters, revealed that both asarinin and thiazolo have a high chance of forming stable protein-ligand complexes with HPV-16 E6, displaying distinct molecular dynamic properties. Thiazolo exhibited superior stability in simulation, evident in ligand conformation and movement graphs, while asarinin excelled in terms of contact residues. Furthermore, SASA, hydrogen bond graphs, and the DCCM graph collectively underscore the comparable potential of both drugs as robust inhibitors of the HPV-16 E6 oncoprotein.

Abstract The Human papillomaviruses type 16 E7 oncoprotein is a 98-amino-acid, 11-kilodalton acidic oncoprotein with three conserved portions. Due to its interaction with the pRb-E2F complex, CKII, CKI (mostly p21), and even HDAC1, it possesses strong transformative and carcinogenic qualities that inhibit normal differentiation and cell cycle regulation. Here, we target the E7 oncoprotein using two prior research active compounds: asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo), and valproic acid as a control. We are performing molecular docking followed by molecular dynamic analysis. By acting as competitive inhibitors in the binding site, it was hypothesized that both drugs would inhibit E7-mediated pRb degradation and E7-mediated p21 degradation, resulting in decreased cell cycle progression, immortalization, and proliferation. In addition, we expect that the direct inhibitory action of valproic acid in E7 will target the CKII-mediated phosphorylation pathway necessary for destabilizing p130 and pRb. According to the results of the dynamic simulation, stable interactions exist between every compound. Despite the instability of E7 protein, stability results indicate that both natural chemicals are preferable, with thiazolo outperforming valproic acid.

Rauvolfia serpentina is widely recognized for its use as a raw material in hypertension and antihypertensive medications, including reserpine. Since this plant is used directly from the natural world, cultivation activities are necessary. Seeds for cultivation must be consistent, high-quality, and free of pests and diseases. Thus, a suitable propagation technique is required. In vitro propagation is one method that can produce homogeneous plants with a relatively high rate of multiplication. Cytokinin-family regulatory molecules are crucial for in vitro proliferation techniques. The aim of this research was to determine the optimal type and concentration of cytokinin for the in vitro induction of R. serpentina shoots. This study employed a completely randomized factorial design. The first factor was the type of cytokinin (Benzylaminopurine (BA), Zeatin, Kinetin, and 2iP), and the second factor was the cytokinin concentration (0, 0.5, 1.0, 1.5 mg/l). Each treatment was replicated 10 times. The results showed that the best cytokinin for R. serpentina shoot induction in vitro was BA at a concentration of 0.5 mg/l. This treatment produced a greater number of shoots and leaves, taller shoots compared to other treatments, and resulted in more well-developed plant visualization.

Nowadays,the development of molecular biology techniques has enabled to engineer drought tolerant sugarcane to accelerate thebreeding program. Dehydrin(DHN)that belong to the group II late embryogenesis abundant (LEA) family is known to havean important role in plant response and adaptation to abiotic stresses (drought, high salinity, cold, heat, etc.). Literature study and bioinformatics analysis reported that DHN1gene on sugarcane showed high homology sequences with sorghum DHN. The expression of DHN1gene on sugarcane var. PSJT 941 treated with various periodof drought stress had been conducted using semi-quantitative reverse transcriptase (RT)-PCR method. The results showed that the expressionlevel of DHN1 geneincreased along withthe increased period of the treatment. The highest expression level of DHN1 gene was resulted from plants that had been subjected to drought for 25 days. Amplification of DHN1gene from plants withthe highest gene expression, resulted an amplicon with a size of 465 bp which representsa full length coding sequence (CDS) of DHN1. Identification using Blast analysis showed that DHN1sequences from sugarcane var. PSJT 941 shared high homology with DHN gene on sugarcane and sorghum. The alignment results also revealed a conserved motif that characterized DHN genes.

Dehydrin (DHN) is known to play an important role in plant response and adaptation to abiotic stresses (drought, high salinity, cold, heat, etc.). Previous research reported the increased expression of DHN in sugarcane stems exposed to drought stress for 15 days which may be controlled by its corresponding stress inducible promoter. The DHN promoter was succesfully isolated from sugarcane variety PSJT 941 (Pr-1DHNSo) and was cloned to pBI121 expression vector fused to a β-glucuronidase (GUS) reporter gene. The aim of this research was the functional testing of the Pr-1DHNSo promoter through transformation into tobacco plant treated with in vitro drought stress. Genetic transformation of Pr-1DHNSo construct was conducted by Agrobacterium tumefaciens. The transformed tobacco was then subjected to drought stress treatment using 40% PEG 6000 for five sequential incubations (0, 12, 24, 48 and 72 hours). The GUS assay reveal that the transformed tobacco treated with drought stress showed a blue color denoting GUS activity in leaf, stem and root tissues and this expression increased along with the length of the drought treatment. The analysis of gusA gene using real time-qPCR normalized to the L25 reference gene also showed that the expression increased in line with the length of time of drought stress. The results presented in this study indicated that the Pr-1DHNSo promoter from sugarcane was expressed and induced by drought stress treatment in tobacco.

Type 2 diabetes mellitus continues to pose a significant global health concern, warranting increased attention. This metabolic disorder is influenced by various factors, such as lifestyle, diet, environment, and genetics. While several approaches have been developed to address the incidence of type 2 diabetes mellitus, current treatments remain inadequate and necessitate further improvement. In this study, our objective was to assess the potential antidiabetic efficacy of anthraquinone glycosides present in rhubarb (specifically physcion diglucoside and aloe-emodin-8- glucoside) as potential inhibitors of the sodium-glucose cotransporter-2. We employed an in silico study to evaluate their inhibitory properties. The computational prediction was performed included the target protein, ligands retrieval, and preparation. Furthermore, the molecular docking process was conducted to assess the interaction between the target protein and ligands. Subsequently, data visualization and analysis were performed. Various indicators were evaluated, including the characteristics of the target molecule and drug candidates, binding affinity scores, interaction positions, types of chemical interactions, amino acid residues involved, hydrophobicity, formation of hydrogen bonds, interpolated charge, and ionizability. These comprehensive evaluations provided valuable insights into the molecular interactions and potential efficacy of the tested compounds. In this computational study, we demonstrated that the both rhubarb anthraquinones, physcion diglucoside and aloe-emodin-8-glucoside, have a great potential as antidiabetic agent by inhibiting the action of the sodium-glucose cotransporter-2. Thus, the inactive the sodium-glucose cotransporter-2 can prevent the excessive number of glucose plasma level in type two diabetes mellitus people. [ABSTRACT FROM AUTHOR]

Diabetes mellitus patients are typically in need of drugs with minimal long-term side effects, leading to an increasing interest in herbal medicine sourced from medicinal plants. Among the available medicinal plants, the fruit of Averrhoa bilimbi L., commonly known as belimbing wuluh, has been recognized for its therapeutic potential and is often used as an alternative medicine for diabetes mellitus. Therefore, this study aims to determine antidiabetic activity of the active fraction of A. bilimbi L. fruit using in vitro and in silico methods and to determine the active compounds contained in the fruit fraction (A. bilimbi L.) based on Liquid Chromatography Mass Spectrometer (LC-MS). LC-MS analysis results showed the presence of 16 organic compounds in the n-hexane fraction, which had the highest IC50 (7.03 µg/mL) antidiabetic activity compared to the ethyl acetate (102.77 µg/mL) and nbutanol (181.65 µg/mL) fractions. In silico molecular docking, analysis was performed for all identified compounds to further support antidiabetic characteristics. Computational predictions showed that 2 A. bilimbi fruit compounds with the greatest RT value, namely 2,3,4,5,6-pentaphenylbenzazocine (-16.0 kcal/mol) and Thraustochytroside A (-6.2 kcal/mol), exhibited higher binding affinity values compared to miglitol (-5.4 kcal/mol). This showed that both compounds had the potential to be developed as a-glucosidase inhibitor alternatives for treating diabetic disorders. [ABSTRACT FROM AUTHOR]

Glucose toxicity become serious risk factor of type 2 diabetes mellitus. Multiple complication can be caused of the abnormal condition of glucose level in blood. Thus, managing the plasma glucose is one of the strategy to minimize the negative effects of type 2 diabetes mellitus. In this present study, we aimed to virtually evaluate the bioactive compounds from Alpinia galanga as inhibitor agent against alpha-glucosidase, which was known as carbohydrate catabolic enzyme. The 2D structure of ligands were retrieved from PubChem database (pubchem.ncbi.nlm.nih.gov/) and were evaluated based on Lipinski rule of five for ensured the druglike-ness standard, while the sequence and 3D structure of target protein, alpha-glucosidase, was retrieved from UniProt database (https://www.uniprot.org/) and was modelled through SWISS-MODEL (swissmodel.expasy.org/). All ligands used in this study then underwent optimization prior to molecular docking and analyzing procedures. According to our prediction results, we found that galangin and 1's-1'-acetoxychavicol acetate which known as bioactive compounds found in A. galanga have significant potency as inhibitor agents against the alphaglucosidase due to its binding affinity scores and other physicochemical properties compared to the anti-diabetic drug, mignitol. Thus, from this finding, we have recent starting point to expand the potency of these bioactive compounds, especially for inhibiting the alphaglucosidase as the novel strategy to reduce the poor prognosis of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Coronaviruses cause mild to severe respiratory infections. The highly contagious SARS-CoV-2 new coronavirus caused a global outbreak of atypical viral pneumonia in late 2019. Acute respiratory distress syndrome, multiple organ failure, respiratory failure, and death can result from the infection. This study aimed to evaluate the possible inhibition activity from numerous medicinal plants' bioactive compounds against three non-structural proteins, namely Nsp1, Nsp2, and Nsp10 of SARS-CoV-2, through the computational study. Molecular docking was performed on the ligands and the target protein. This study investigated multiple criteria, including binding affinity value, location, and chemical interaction. In this present study, we found the top three highest binding affinity values of bioactive compounds against Nisp1, namely cafestol, crocin, and ledene; the top three highest binding affinity values of bioactive compounds against Nisp2, including cafestol, kahweol, and theaflavin 3,3'-digallate; and top three highest binding affinity value of bioactive compounds against Nisp10 namely cafestol, kahweol, and theaflavin-3,3'-digallate. Interestingly, we also found that cafestol, crocin, and theaflavin-3,3'-digallate binds to all target proteins. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most prevalent form of cancer in Indonesia. HPV16 and HPV 18 are the leading causes of cervical cancer, accounting for 70-90% of cases. The E5 protein may play a critical role in the disease’s development. Although the high-risk (HR) version of this protein may have some benefits in evading the immune system through MHC I and influencing the cell cycle via p21/p27, very few studies have been performed owing to its tiny size and high hydrophobicity. The purpose of this research is to predict the anti-viral activity of asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo) using molecular docking and molecular dynamics. The docking results showed that the two candidate drugs had a lower docking affinity than rimantadine but comparable stability. Both potent compounds are predicted to disrupt MHC I localization in the ER, the ability of infected cells to proliferate, and the virion assembly process. In contrast, rimantadine is predicted to disrupt infected cells’ proliferation ability via the epidermal growth factor receptor (EGFR) regulation and inhibit the activation process of mitogenic signalling in keratinocytes. [ABSTRACT FROM AUTHOR]