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Various components of the tobacco plant (Nicotiana tabacum L.) have undergone pharmacological assessment to highlight their traditional role in addressing different health conditions. The anti-inflammatory properties of thirteen natural substances were investigated through the use of molecular docking conducted with AutoDock 4.2.6 Tools and Molecular Dynamics Simulations (MDS) executed with GROMACS 2016.3. ADME characteristics were assessed using SwissADME (absorption, distribution, metabolism, and excretion). Chlorogenic acid and rutin, plant-derived natural compounds, showed substantial binding tendencies with cyclooxygenase-1 (COX-1), phosphodiesterase-4 (PDE4), cyclooxygenase-2 (COX-2), phosphodiesterase-7 (PDE7), interleukin-17A (IL-17A), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and prostaglandin F synthase. Rutin emerged as the most notable among the tested compounds (docking energy: −11.0 kcal/mol against PDE7 and prostaglandin F synthase). Chlorogenic acid also displayed substantial and noteworthy binding energies of −9.4 kcal/mol with PDE4 and PDE7 receptors. Consequently, these investigated natural compounds could potentially serve as agents that reduce inflammation and require additional in vitro and in vivo studies to aid the creation of new anti-inflammatory drugs.

Helminth infections can be effectively treated with various anthelmintics. However, the potential for drug resistance and the need for repeated doses to ensure successful treatment are some limitations to the treatment. This study aimed to evaluate the ability of phytochemicals from Syzygium aqueum to inhibit ATP-dependent 6-phosphofructokinase (6-PFK) from Ascaris lumbricoides and Ascaris suum using the in silico method (molecular docking, molecular dynamics simulation, and ADMET analysis) and in vitro evaluation using mortality, paralysis, and ovicidal activity testing. Molecular docking outcomes indicated that out of 76 compounds from Syzygium aqueum, 18 molecules exhibited strong inhibition against the target enzyme, based on binding free energy and interaction patterns. Molecular dynamics simulation demonstrated that samarangenin A and butyrospermol complexes remained stable for up to 200 ns within a range below 1 nm. The most promising compounds also exhibited good ADMET properties. In the in vitro egg hatch test, a 10% concentration of Syzygium aqueum extract showed potent ovicidal properties by significantly reducing the number of fertile eggs but was less effective than 0.12% albendazole. However, ferulic acid at various concentrations exhibited minimal effect on egg fertility but showed increased mortality and incidence of paralysis at higher doses against male worms. These findings yielded valuable insights into the underlying mechanisms, providing essential clues for the development of highly efficient inhibitors for parasitic worm infections through structure-based design.

Emerging clinical observations underscore the correlation between interleukin-8 (IL-8) and rosacea. Increased IL-8 expression has been detected in rosacea samples, particularly in moderate to severe manifestations. This phenomenon has prompted the exploration of IL-8 as a prospective therapeutic target for rosacea treatment. To this end, a selection of compounds sourced from the ZINC database, encompassing six small molecules, was made with the intent of identifying promising lead candidates that exhibit drug-like characteristics against IL-8. Through an integrated in silico approach involving structure-guided drug design, encompassing molecular docking, molecular dynamics (MD) simulation, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis, protein-peptide docking, and scrutiny of toxicity profiles, it was ascertained that the small molecule ZINC000022339916 effectively inhibits IL-8 activity. These findings present a novel lead compound that warrants further validation through in vitro, in vivo, and ongoing clinical investigations to confirm its potential for therapeutic management of rosacea.

In the effort to combat SARS-CoV-2 infection, researchers are currently exploring the repurposing of conventional antiviral drugs, despite their limited efficacy. The SARS-CoV-2 virus encodes a papain-like protease (PLpro), which not only plays a crucial role in viral replication but also cleaves ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins, making it a prime target for the development of new antiviral medications. In this study, we conducted a multi-step in silico screening to identify novel, noncovalent PLpro inhibitors. Curcumin, an antioxidant derived from turmeric rhizomes (Curcuma longa L.), has undergone extensive preclinical investigations and shown significant efficacy against viruses and other ailments in both laboratory and animal studies. However, the pharmacological limitations of curcumin have prompted the synthesis of numerous novel curcumin analogs, necessitating evaluation for their therapeutic potential. The selectivity of the top-scoring compounds was assessed through molecular docking studies and molecular dynamics simulations to determine their binding affinity to PLpro. As a result, we identified 20 potential, selective PLpro inhibitors, from which the top two compounds (THA111 and THHGV6) were selected based on their binding free energy values towards PLpro as estimated by MM-PBSA calculations. These selected candidates demonstrate promising activity against the protein, with binding free energy values ranging from approximately −105 to −108 kJ/mol, and largely adopt a similar binding mode to known noncovalent SARS-CoV-2 PLpro inhibitors (GRL0617 = −100.98 kJ/mol). We further propose these two most promising compounds for future in vitro evaluation. The findings for the top potential PLpro inhibitors have been deposited in a database (Curcumin Research Center) to aid research on anti-SARS-CoV-2 drugs.

Background: Alpha mangostin (AM) has demonstrated significant potential as an anticancer agent, owing to its potent bioactivity. However, its clinical application is limited by poor solubility, which hampers its bioavailability and effectiveness. Amorphous solid dispersion (ASD) presents a promising technique to enhance the solubility and stability of AM. Molecular dynamics simulation offers a rapid, efficient, and precise method to evaluate and optimize ASD formulations before production. Aim of Study: In this study, we conducted molecular dynamics simulations to explore the ASD development of AM with poloxamer and pullulan. Result: Our results revealed that AM–poloxamer complexes exhibit superior interaction characteristics compared to AM–pullulan, with a 1:5 ratio of AM to poloxamer and a cooling rate of 1 °C/ns demonstrating the most favorable outcomes. This combination showed enhanced hydrogen bonding, a more compact molecular structure, and higher stability, making it the optimal choice for ASD formulation. Conclusion: The integration of molecular dynamics simulation into ASD development significantly accelerates the formulation process and provides critical insights into achieving a stable and effective AM dispersion. The AM–poloxamer complex, particularly at a 1:5 ratio with a 1 °C/ns cooling rate, offers the best potential for improving AM solubility and therapeutic efficacy.

The growth of micro-organisms that acquire resistance to most commercially available antibiotics is occurring rapidly. Consequently, a pressing necessity exists to identify and detect new antimicrobial substances. This study aimed to analyze the antioxidant and antibacterial activity of nanoemulsion clove extract and grape seed oil. This research was conducted in June 2023 using experimental methods at the Research Laboratory of the Universitas Islam Bandung Pharmaceutical Study Program by developing a nanoemulsion preparation containing clove extract (Syzygium aromaticum L.) and grape seed oil (Vitis vinifera L.). Antioxidant activity was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Antibacterial activity was tested using the agar diffusion method by measuring the growth inhibitory diameter of Staphylococcus aureus and Streptococcus mutans bacteria and divided into four groups formulas based on the addition of clove extract with different concentrations in the nanoemulsion base (FA=0.25%, FB=0.5%, FC=0.75%, and FD=1%) to see the best results. The result shows nanoemulsion preparations have antioxidant properties in the DPPH test. The FA formula has the highest IC50, namely 1,117.56 ppm. The antibacterial activity of Staphylococcus aureus and Streptococcus mutans has an inhibition zone, although it is still in the category of inhibiting bacterial growth, but does not kill growth. The nanoemulsion formulation, comprising clove extract and grape seed oil, has exhibited exceptional antioxidant properties and substantial antimicrobial efficacy against prevalent oral bacterial strains.

The human body naturally has an antioxidant system to counteract free radical reactivity in a sustainable manner, but if the number of free radicals in the body is excessive, additional antioxidants are needed from food intake, namely vitamin C, vitamin E, carotenes and flavonoids. One plant that has the potential as an antioxidant is Ziziphus spina-christi (ZSC) because it contains phenolics and flavonoids. This study aims to determine the flavonoid content both qualitatively and quantitatively and to test the antioxidant activity of ZSC leaf extract using in vitro and in silico attenuation methods. Determination of the total flavonoid content of ZSC leaf extract using a comparison of quercetin. In vitro the antioxidant activity assay of ZSC leaf extract was carried out by measuring the reducing activity of ZSC leaf extract against the radical DPPH using ascorbic acid as a comparison, while the in silico method used QSAR and pharmacophore modelling techniques. The results showed that the total flavonoid content obtained from ZSC leaf extract was 0.2515 ± 0.0013 mg QE/g D.W with an IC50 of 58.9296 ppm. Furthermore, from the in silico method using pharmacophore modeling and QSAR techniques, 8 hit compounds were obtained from the content of ZSC with IC50 QSAR ranging from 6.57 μM to 0.0004 μM, which was thought to be the metabolite that had the most role in its antioxidant activity. This value indicates that ZSC leaf extract has potential as a very strong antioxidant. ZSC leaf extract can be used as an antioxidant candidate in drug and cosmetic preparations through the oral or percutaneous route. It also proves that QSAR and pharmacophore modelling techniques can be used as confirmatory tests for in vitro results in determining the antioxidant activity of natural materials.

Coronavirus 19 (COVID-19) is still a global health issue to date, SARS-CoV-2 is a novel coronavirus that is responsible for this sickness. The receptor-binding domain of the SARS-CoV-2 virus associates with angiotensin-converting enzyme 2 (ACE-2) and allows the virus to enter human cells. Natural peptides such alpha-defensin are thought to attach to the SARS-CoV-2 RBD and prohibit it from engaging with ACE-2. Molecular dynamics simulations using a computational approach are utilized to understand the stability of six alpha-defensin macromolecules using the Gromacs 2016 software. The trajectories formed are then analyzed using VMD 1.9.4 and BIOVIA Discovery Studio 2020 software. Finally, the free energy is estimated using the MM/PBSA method. The alpha-defensins 2 macromolecules were found to have the best stability based on numerous study results (trajectory visualization, RMSD, RMSF, and free energy calculations). As a result, these macromolecules could be used to build new antiviral treatments for COVID-19 infectious disease candidates.

As the Seram Laut Island (SLI) community relies on coral fish resources, changes in coral fish populations will impact their income and nutritional needs. This research aimed to investigate the SLI ecosystem's status using risk score indicators and the management implications for the sustainability of the coral fish fishery ecosystem. This research used the tier 2 approach semiquantitative ecosystem-based fishery assessment (EBFA) method based on a risk score of 0 to 3, with four objectives: sustainability, habitat, biodiversity, and socio-economy. Several high-risk scores in the red zone were found in the fishing efforts indicator of Lethrinus obsoletus, Siganus canaliculatus, and Cephalopolis miniata, catch per unit effort (cpue) indicator of S. canaliculatus, maturity proportion, and fishing gear impact of L. obsoletus and S. canaliculatus and habitat quality indicator of S. canaliculatus. Coral fish's species risk index (SRI) ranged from 1.28 to 1.64 (yellow zone), with L. obsoletus having the highest SRI. The coastal of SLI's ecosystem risk index was in the limited range (yellow zone). For ecosystem sustainability, proper management should be developed with a focus on the indicators in the high-risk state (red zone) by spatial planning for coral and habitat conservation, as well as policies based on local wisdom.

Background: Alpha mangostin (AM) has demonstrated significant potential as an anticancer agent, owing to its potent bioactivity. However, its clinical application is limited by poor solubility, which hampers its bioavailability and effectiveness. Amorphous solid dispersion (ASD) presents a promising technique to enhance the solubility and stability of AM. Molecular dynamics simulation offers a rapid, efficient, and precise method to evaluate and optimize ASD formulations before production. Aim of Study: In this study, we conducted molecular dynamics simulations to explore the ASD development of AM with poloxamer and pullulan. Result: Our results revealed that AM–poloxamer complexes exhibit superior interaction characteristics compared to AM–pullulan, with a 1:5 ratio of AM to poloxamer and a cooling rate of 1 °C/ns demonstrating the most favorable outcomes. This combination showed enhanced hydrogen bonding, a more compact molecular structure, and higher stability, making it the optimal choice for ASD formulation. Conclusion: The integration of molecular dynamics simulation into ASD development significantly accelerates the formulation process and provides critical insights into achieving a stable and effective AM dispersion. The AM–poloxamer complex, particularly at a 1:5 ratio with a 1 °C/ns cooling rate, offers the best potential for improving AM solubility and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Citrus peels contain various phytochemical active compounds such as flavonoids that are useful for antiaging cosmetic products. This study was conducted to identify the anti-collagenase and anti-elastase activities of flavonoid compounds in citrus peel and to determine the molecular interaction mechanism using the molecular docking method. The study was carried out through several stages, including preparation of enzyme macromolecules, preparation of flavonoid compound molecules, validation of molecular docking, identification of binding-free energy, visualization of interaction conformations, and predictions of molecular skin toxicity. The result showed that the flavonoid compounds in citrus peel (hesperidin, naringin, nobiletin, and tangeretin) could bind to collagenase and elastase enzymes. Naringin has the highest affinity for the collagenase enzyme with the binding-free energy of −9.52 kcal/mol, while nobiletin has the highest affinity for the elastase enzyme with the binding-free energy of −6.44 kcal/mol. Compared to EGCG (epigallocatechin gallate), the flavonoid compounds have a lower affinity for the collagenase enzyme but a higher affinity for elastase enzymes. Hydrogen bonds and the hydrophobic interactions dominate the interaction between citrus peel’s flavonoids against the enzymes. When applied to the skin, flavonoid compounds are predicted to have no risk of skin toxicity. The flavonoid compounds of citrus peels are expected to have anti-collagenase and anti-elastase activities.

The 2019 coronavirus pandemic disease (COVID-19) is still declared a global pandemic by the World Health Organization (WHO). Therefore, an effort that is considered effective in finding therapeutic agents is needed to prevent the spread of COVID-19 infection. One of the steps that can be chosen is by utilizing antimicrobial peptides (AMPs) from animal venom by targeting the specific receptor of SARS-CoV-2, namely the main protease (Mpro). Through this research, a computational approach will be conducted to predict antiviral activity, including protein-peptide docking using PatchDock algorithm, to identify, evaluate, and explore the affinity and molecular interactions of four types of antimicrobial peptides (AMPs), such as Mucroporin, Mucroporin-M1, Mucroporin-S1, and Mucroporin-S2 derived from scorpion venom (Lychas mucronatus) against main protease (Mpro) SARS-CoV-2. These results were then confirmed using protein-peptide interaction dynamics simulations for 50 ns using Gromacs 2016 to observe the molecular stability to the binding site of SARS-CoV-2 Mpro. Based on protein-peptide docking simulations, it was proven that the Mucroporin S-1 peptides have a good affinity against the active site area of SARS-CoV-2 Mpro, with an ACE score of −779.56 kJ/mol. Interestingly, Mucroporin-S1 was able to maintain the stability of its interactions based on the results of RMSD, RMSF, and MM/PBSA binding free energy calculations. The results of the computational approach predict that the Mucroporin-S1 peptide is expected to be useful for further research in the development of new antiviral-based AMPs for the COVID-19 infectious disease.

Tyrosinases are essential metal-containing enzymes in the biosynthesis of melanin, therefore responsible for pigmentation of the skin. The upregulation of tyrosinase enzyme activities leads to hyperpigmentation that will become a health problems and interfere psychosocially. Inhibition of tyrosinase enzyme activity, both competitive and non-competitive become widely developed for most anti hyperpigmentation agent. Natural antioxidants are one of the potential compounds for this purpose. Red grape seeds contain high levels of antioxidant compounds, such as procyanidin, prodelphinidin, and propelargonidin. In this research in silico studies, including molecular docking, molecular dynamics simulations, and toxicity predictions, were used to assess the activity of the three molecules of polyphenolic compounds on macromolecules of the tyrosinase enzyme. Molecular docking studies show that the compound propelargonidin has the highest affinity against the macromolecule of the tyrosinase enzyme, with a binding free energy value of −32.87 kJ/mol. These results were confirmed in molecular dynamics simulations that show strong interactions at the macromolecular active site of the tyrosinase enzyme. Toxicity prediction results show that the three polyphenolic compound molecules were classified in the High-Class Category, which shows that safety is not guaranteed, but is likely, not carcinogenic and nongenotoxic. Therefore, the compound propelargonidin is predicted to be able to interact strongly with the tyrosinase enzyme. The results in this research are useful for further study in the development of tyrosinase enzyme inhibitors.

Coronavirus infection (COVID-19) caused by SARS-CoV-2 appears as a pandemic that has spread to almost all countries in the world. Antiviral therapy using natural compounds is one alternative approach to overcome this infectious disease. The therapeutic mechanism is proven effective against the main protease (Mpro) of SARS-CoV-2. This research aims to perform bioinformatics studies, including ligand-docking simulations and protein-protein docking simulations, to identify, evaluate, and explore five compounds' activity on SARS-CoV-2 Mpro and their effects against Angiotensin-Converting Enzyme 2 (ACE-2). Protein-ligand docking simulations show kaempferol, flavonol, and their glycosides (Afzelin and Juglanin) and other flavonoids (Quercetin, Naringenin, and Genistein) have a high affinity towards SARS-CoV-2 Mpro. These results were then confirmed using protein-protein docking simulations to observe the ability of five compounds to prevent the attachment of ACE-2 to the active site. Based on the results of the bioinformatics studies, Quercetin has the best affinity, with a binding free energy value of −33.18 kJ/mol. The five compounds are predicted to be able to interact strongly with SARS-CoV-2. The results in this research are useful for further studies in the development of novel anti-infective drugs for COVID-19 that target SARS-CoV-2 Mpro.

The COVID-19 has spread worldwide and become an international pandemic. The promising target for drug discovery of COVID-19 was SARS-CoV-2 Main Protease (Mpro), that has been successfully crystallized along with its inhibitor. The discovery of peptide-based inhibitors may present better options than small molecules for inhibitor SARS-CoV-2 Mpro. Natural compounds have such a wide potential and still few explored, Zizyphus spina-christi is one of the medicinal plants that have many pharmacological activities and contains a peptide compound from alkaloids class, i.e. cyclopeptide alkaloids, that is interesting to explore as SARS-CoV-2 Mpro inhibitor. The compound structure was drawn and optimized using density functional theory 3-21G method. The protein chosen was the high resolution of SARS-CoV-2 MPro receptor (1.45 Å) with PDB ID: 6WNP, in complex with boceprevir. Molecular docking simulation was performed using Autodock4 with 100 numbers of GA run, the validation methods assessed by RMSD calculation. Furthermore, the prediction of pharmacological activity spectra was carried out using the PASS Prediction server. The results showed RMSD value was 1.98 Å, this docking method was valid. The binding energy of all compounds showed better results than the native ligand (Boceprevir). The in silico PASS prediction results indicated that all compounds showed antiviral activity. Some compounds showed protease inhibitory activity, i.e Ambiphibine-H, Franganine, and Mauritine-A, and the highest Pa (Predicted activity) value showed by Mauritine-A compounds. It can be concluded that the cyclopeptide compounds of Zizyphus spina-christi were indicated to have a potential as COVID-19 therapy targeting SARS-CoV-2 Mpro.

Resistensi antibiotika muncul sebagai polemik yang dapat mempengaruhi kesehatan manusia. Kemajuan teknologi membuka peluang dalam penemuan molekul senyawa baru yang mampu mencegah perkembangan mikroba patogen, seperti Pseudomonas aeruginosa yang resisten terhadap beberapa jenis antibiotika. Terapi fotodinamika dengan memanfaatkan penggunaan fotosensitizer yang berasal dari senyawa yang membentuk kompleks dengan besi merupakan salah satu pendekatan alternatif untuk mengatasi penyakit infeksi dengan risiko resistensi mikroba yang lebih rendah. Penelitian yang dilakukan secara in silico ini bertujuan untuk mengamati, mengeksplorasi, dan mengevaluasi mekanisme aksi berbasis struktural dari molekul senyawa yang membentuk kompleks dengan besi, yaitu besi-ftalosianina dan besi-salofen terhadap protein hemofor HasAp serta pengaruh molekularnya terhadap bagian situs aktif pengikatan dari protein hemofor HasR. Identifikasi interaksi molekuler dan afinitas antara molekul senyawa besi-ftalosianina dan besi-salofen terhadap protein hemofor HasAp dilakukan dengan simulasi ligan-protein docking mempergunakan software MGLTools 1.5.6 yang dilengkapi dengan AutoDock 4.2. Di samping itu, dilakukan juga simulasi protein-protein docking terhadap sistem kompleks ligan-protein untuk memastikan pengaruh molekularnya terhadap bagian situs aktif pengikatan dari protein hemofor HasR dengan mempergunakan software PatchDock. Berdasarkan simulasi ligan-protein docking diperoleh hasil bahwa senyawa besi-ftalosianina memiliki afinitas paling baik terhadap kedua protein hemofor HasAp, dengan nilai energi bebas pengikatan masing-masing sebesar −68,45 kJ/mol dan −65,23 kJ/mol. Menariknya, hasil simulasi protein-protein docking antara kompleks molekul senyawa besi-ftalosianina dan protein hemofor HasAp-besi-ftalosianina terhadap protein hemofor HasR memiliki nilai energi kontak atom yang positif sebesar 556,56 kJ/mol. Dari penelitian ini dapat diprediksikan bahwa perbedaan struktur molekul senyawa yang membentuk kompleks dengan besi mampu mempengaruhi mekanisme aksi berbasis structural terhadap protein hemofor target.

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The role of in silico studies in the discovery of new drugs is very important and interesting in the recent years, where the results can be used as confirmation of the results of in vitro tests carried out experimentally in the laboratory. One of the herbal ingredients is Ziziphus spina-christi leaves with effective antibacterial activity, such as for acne-causing bacteria, namely Propionibacterium acnes. This is because it contains main secondary metabolites with saponins as the major components which contain christinin as its active compound. There are four known types of christinin, namely christinin-A, christinin-B, christinin-C, and christinin-D. In this study, the molecular interaction of the christinin compound was tested to predict its affinity for Propionibacterium acnes compared to clindamycin, as well as to determine the level of safety on the skin so that it can be applied as a topical anti-acne dosage form. In silico studies, including molecular docking and toxicity prediction, were used to assess the activity of four molecules of the christinin compound on c-Jun N-terminal kinase (JNK) macromolecules. The christinin molecules form a strong and stable molecular interaction with the active site of the binding of c-Jun N-terminal kinase (JNK) macromolecules. Interestingly, the christinin compound molecules also has a fairly good level of safety based on the three identified parameters. Based on this results christinin compound molecules has potential to be developed as c-Jun N-terminal kinase (JNK) inhibitors candidate to control of skin infections caused by Propionibacterium acnes which has potential as a topical anti-acne.