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This study investigates the effects of natural inhibitors (pomegranate, algae, and tomato extracts) on the corrosion resistance of titanium (grade 2). To deepen understanding the inhibition mechanism, Molecular Dynamic (MD) and Monte Carlo (MC) simulations were employed to analyze adsorption behaviors and identify optimal adsorption sites on titanium oxide (TiO2) surfaces for compounds within the inhibitors. Results indicate non-flat adsorption orientations, with pomegranate peel extract components showing superior inhibition capabilities, attributed to the formation of strong O-H chemical bonds with the TiO2 surface. In the experimental part of the study Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PDP) were conducted. Two electrolytes were tested: a solution 3.5% NaCl and a solution 0.5 M NaOH. All the tests were performed with 5% of inhibitor and with the reference solution. Also, inhibition efficiency was calculated on the base of PDP tests. The study found that pomegranate extract can act as a good corrosion inhibitor for titanium alloy in aqueous solutions 0.5 M NaOH. This was demonstrated by the increase in the corrosion potential and impedance modulus and decrease in the corrosion current density after the addition of pomegranate extract to the solution. However, in a 3.5% NaCl solution, the efficacy of pomegranate extract was less pronounced, probably due to the high aggressivity of the electrolyte. Tomato and algae extract have instead shown very low inhibition effects in all the tested conditions. [ABSTRACT FROM AUTHOR]

One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal actin assembly, phenotypic signalling, and transcription process which affects a wide range of cellular processes such as cell motility, invasion, metastasis, cell growth, angiogenesis, and cell cycle progression. Most recently, PAK1 was shown to be involved in the progression of coronavirus-caused pulmonary inflammation (lung fibrosis), but clinical data is not currently available yet. This review highlights the naturally occurring compounds that inhibit the oncogenic, melanogenic, and ageing kinase PAK1. Additionally, the potent anti-inflammatory effects of natural products in an attempt to prevent pulmonary fibrosis in COVID-19 have also been discussed. [ABSTRACT FROM AUTHOR]

Drinking water quality and the commercial value of aquatic items are both significantly impacted by odor molecules like 2-methylisoborneol (2-MIB) and geosmin (GSM). Many investigations have been conducted to identify the microorganisms involved in the synthesis of 2-MIB and GSM. However, few studies have attempted to identify potential degradation factors in the natural environment. Here, pathway analysis of the relationship between water quality parameters and the distribution of odor compounds in water bodies led to a more significant connection (p < 0.05) between total nitrogen, total phosphorus, chemical oxygen demand, and salinity in water bodies for the distribution of their odor compounds. Salinity among them exhibited the strongest connection and had a direct impact. The establishment of a larger spatial scale statistical research method, mainly using the water environment with different salinities formed in different geographical areas, and the distribution of odor compounds in this water body as a research vehicle helped to find the most concise relationship between the two variables. The results show that the concentration of odor compounds is lower in waters with higher salinity, which proves the negative correlation between the two. The results of this study provide a theoretical basis for solving the problem of odorous pollutants in water bodies, with the aim of improving the utilization of water resources more effectively and, secondly, leading to a new guiding direction for the conservation and exploitation of impact plains and mudflats. [ABSTRACT FROM AUTHOR]

Mild steel corrosion adversely impacts various industries, specially in acidic environments, leading to reduced metal efficiency. This study explored the efficacy of mango leaves crude ethanolic extract (MLCEE) as a natural corrosion inhibitor for mild steel. Different concentrations, such as treatment 1 (25%), treatment 2 (50%), treatment 3 (75%), and treatment 4 (100%) MLCEE, were tested, along with a commercial inhibitor (WD-40). The dilution method was utilized to obtain the concentrations and acid/base solutions. The mild steel plate was cut and pre-treated through rapid thermal annealing. The mild steel was then immersed in 1M HCl and 1M NaOH for its corrosion test. Gravimetric weight loss was computed and statistically analyzed using one-way ANOVA and Tukey's HSD Test to determine the treatments’ effectiveness, revealing that the 100% concentration significantly differed from other treatments in both mediums, where it had a p-value of 0.00. Treatment 4 yielded no significant change in the weight of mild steel before (5.05 g) and after (5.01 g) immersion in HCl, and in weight before (4.65 g) and after (4.61 g) immersion in NaOH, as shown in the paired sample ttest, thus it indicates its potential as a metal coating against corrosion activity. This implied that MLCEE is capable of inhibiting corrosion inhibition and can withstand aggressive media. These results may become a basis for future studies covering metal corrosion and plant extract utilization. However, different annealing processes may be considered to promote better adsorption, and other parameters may be added to further explore the efficacy of MLCEE as a potential corrosion inhibitor.

This study investigates the effects of natural inhibitors (pomegranate, algae, and tomato extracts) on the corrosion resistance of titanium (grade 2). To deepen understanding the inhibition mechanism, Molecular Dynamic (MD) and Monte Carlo (MC) simulations were employed to analyze adsorption behaviors and identify optimal adsorption sites on titanium oxide (TiO2) surfaces for compounds within the inhibitors. Results indicate non-flat adsorption orientations, with pomegranate peel extract components showing superior inhibition capabilities, attributed to the formation of strong O-H chemical bonds with the TiO2 surface. In the experimental part of the study Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PDP) were conducted. Two electrolytes were tested: a solution 3.5% NaCl and a solution 0.5 M NaOH. All the tests were performed with 5% of inhibitor and with the reference solution. Also, inhibition efficiency was calculated on the base of PDP tests. The study found that pomegranate extract can act as a good corrosion inhibitor for titanium alloy in aqueous solutions 0.5 M NaOH. This was demonstrated by the increase in the corrosion potential and impedance modulus and decrease in the corrosion current density after the addition of pomegranate extract to the solution. However, in a 3.5% NaCl solution, the efficacy of pomegranate extract was less pronounced, probably due to the high aggressivity of the electrolyte. Tomato and algae extract have instead shown very low inhibition effects in all the tested conditions.

Plants are considered excellent resources for the generation of greener biomaterials. Plant extract are renewable in nature. Various metabolites present in plant extract are normally used in redox reaction for the formation of eco-friendly nano-particles. It is also considered as the main factory for the green synthesis of metal nano-particles. The plant-based nano-particles is very necessary for absolute harmony connection between plant science and nanotechnology. Ashwagandha is the non-toxic herb which used to treat a range of conditions and its life changing benefits runs over a long time. Its numerous medicinal values make this plant so popular. It is a stress buster which works for all "SUPERHERB". This super herb rejuvenates our body and brain from the inside out. Present review depicts the variety of assistance of Ashwagandha plant with or without nanoparticles, from the past to the present time of corona. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 main protease (Mpro) is an attractive target for drug discovery. Methods: A pharmacophore model was built using the three-dimensional (3D) pharmacophore generation algorithm HypoGen in Discovery Studio 2019. The best pharmacophore model was selected for validation using a test set of 24 compounds and was used as a 3D query for further screening of an in-house database of natural compounds. Lipinski's rule of five was used to assess the drug-like properties of the hit compounds. The filtered compounds were then subjected to bioactivity evaluations. The active compounds were docked into the active site of the SARS-CoV-2 Mpro crystal structure (PDB ID: 7D1M). Results: A suitable 3D pharmacophore model, Hypo1, was found to be the best model, consisting of four features (one hydrophobic feature, one hydrogen bond donor, and two hydrogen bond acceptors). Pharmacophore-based virtual screening with Hypo1 as the query to search an in-house database of 34 439 natural compounds resulted in 1502 hits. Among these, 255 compounds satisfied Lipinski's rule of five. The highest ranking 10 compounds were selected for further experimental testing, and one hit (W-7) illustrated inhibitory activity against SARS-CoV-2 Mpro with an IC50 value of 75 μM. Docking studies revealed that this hit compound retained the necessary interactions within the active site of SARS-CoV-2 Mpro. Conclusion The identified lead natural compound could provide a scaffold for the further development of SARS-CoV-2 Mpro inhibitors. [ABSTRACT FROM AUTHOR]

Cathepsin L (CTSL), a cysteine cathepsin protease of the papain superfamily, plays a crucial role in cancer progression and metastasis. Dysregulation of CTSL is frequently observed in tumor malignancies, leading to the degradation of extracellular matrix and facilitating epithelial-mesenchymal transition (EMT), a key process in malignant cancer metastasis. This review mainly provides a comprehensive information about recent findings on natural inhibitors targeting CTSL and their anticancer effects, which have emerged as potent anticancer therapeutic agents or metastasis-suppressive adjuvants. Specifically, inhibitors are categorized into small-molecule and macromolecule inhibitors, with a particular emphasis on cathepsin propeptide-type macromolecules. Additionally, the article explores the molecular mechanisms of CTSL involvement in cancer metastasis, highlighting its regulation at transcriptional, translational, post-translational, and epigenetic levels. This work underscores the importance of understanding natural CTSL inhibitors and provides researchers with practical insights to advance the relevant fields and discover novel CTSL-targeting inhibitors from natural sources. [Display omitted] • Extracellular cathepsin L (CTSL) plays a crucial role in cancer metastasis. • Altered dynamics of CTSL contribute to abnormal epithelial-mesenchymal transition. • Recent information for CTSL and CTSL inhibitors from natural products is reviewed. • Inhibitors are reviewed by dividing them into small-molecules and macromolecules. • Molecules selectively targeting CTSL can effectively suppress cancer metastasis. [ABSTRACT FROM AUTHOR]

Main protease (Mpro) plays a key role in replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was designed for finding natural inhibitors of SARS-CoV-2 Mpro by in silico methods. To this end, the co-crystal structure of Mpro with telaprevir was explored and receptor-ligand pharmacophore models were developed and validated using pharmit. The database of "ZINC Natural Products" was screened, and 288 compounds were filtered according to pharmacophore features. In the next step, Lipinski's rule of five was applied and absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the filtered compounds were calculated using in silico methods. The resulted 15 compounds were docked into the active site of Mpro and those with the highest binding scores and better interaction including ZINC61991204, ZINC67910260, ZINC61991203, and ZINC08790293 were selected. Further analysis by molecular dynamic simulation studies showed that ZINC61991203 and ZINC08790293 dissociated from Mpro active site, while ZINC426421106 and ZINC5481346 were stable. Root mean square deviation (RMSD), radius of gyration (Rg), number of hydrogen bonds between ligand and protein during the time of simulation, and root mean square fluctuations (RMSF) of protein and ligands were calculated, and components of binding free energy were calculated using the molecular mechanic/Poisson-Boltzmann surface area (MM/PBSA) method. The result of all the analysis indicated that ZINC61991204 and ZINC67910260 are drug-like and nontoxic and have a high potential for inhibiting Mpro. [ABSTRACT FROM AUTHOR]

Several species of reptiles and mammals have components in their sera that can neutralize toxic components present in snake venoms. In this manuscript, we studied the neutralizing capacity of Chaco eagle's (Buteogallus coronatus) serum. This South American bird of prey eats snakes as a regular part of its diet and has anatomical features that protect from snakes' bites. The neutralizing potency of the Chaco eagle's serum was tested on lethal, hemorrhagic, procoagulant, and phospholipase activities of the venom of "yarará grande" (Bothrops alternatus) and on phospholipase activity of "yarará ñata" (Bothrops ammodytoides) venom; both snakes are known to be the prey of Chaco eagle. Sera of crested caracara (Caracara plancus- a scavenger, omnivorous pan-American bird of prey), secretary bird (Saggitarius serpentarius- an omnivorous bird of prey from Africa that can include venomous snakes in its diet), common hen (Gallus gallus), rat (Rattus norvegicus), mouse (Mus musculus), horse (Equus caballus), and dog (Canis lupus familiaris) were also tested to compare the inhibitory capacity of neutralization. To test isologous and xenologous neutralization, sera from Bothrops alternatus and white-eared opossum (Didelphis albiventris), respectively, were used due to their known inhibitory activity on Bothrops venoms. As a control for the neutralization activity, antibothropic antivenom was used. Chaco eagle's serum neutralized hemorrhagic and phospholipasic activity and slightly neutralized the coagulation and the lethal activity of Bothrops spp. venom. The neutralizing capacity was present in the non-immunoglobulin fraction of the serum, which showed components of acidic characteristics and lower molecular weight than IgY, in correspondence with the characteristics of PLA 2 s and SVMPs inhibitors described in sera from some snakes and mammals. These studies showed that Chaco eagle's serum neutralizes all toxic activities tested at a higher level than sera from animal species in which inhibitors of snake venoms have not been described (p < 0.05), while it is lower or similar in neutralizing capacity to white-eared opossum and B. alternatus sera. [Display omitted] • Chaco eagle serum neutralizes some activities of Bothrops venoms. • Phospholipase activity of B. alternatus and B. ammodytoides was neutralized. • Hemorrhagic activity of B. alternatus was neutralized. • The neutralizing activity was not dependent of immunoglobulins. • Fractions that neutralizes have some similarities with known SVMPIs and SVPLIs. [ABSTRACT FROM AUTHOR]

Single cell oil (SCO) produced by yeast is an attractive alternative due to higher yield of lipid in a limited space with opportunity for naturally manipulating its quality. In the present study, the banana peel is used as a source of carbon for biotransformation by Rhodotorula mucilaginosa to lipid. Further, the quality and quantity of the lipid are enhanced using discarded aqueous Prosopis cineraria pod extract as a natural inhibitor. Prosopis cineraria aqueous extract was quantified using HPLC to contain phenylpropenoids such as epicatechin (0.068%), gallic acid (0.29%), quercetin (0.34%), epigallocatechin (0.091%), rutin (0.141%), ellagic acid (0.141%), along with glucose (1.22%), and sucrose (2.36%). The sucrose and glucose were isolated from the aqueous extract, and further characterized through NMR and TGA. Hence, this natural inhibitor is found expedient as compared to the chemical inhibitor (statin) in terms of lipid production with desirable quality. It is achieved by inhibitors blocking of yeast competitive mevalonate pathway to promote higher lipid accumulation in the microbial cells. The anti-cholestrolemic activity of this natural inhibitor might be influenced lipid accumulation by blocking the mevalonate pathway. Thus, the reducing sugars as well as phenylpropenoids were worked in synergy to enhance the accumulation of unsaturated lipid in the microbial cells. Phenylpropenoids may inhibit the key enzyme HMG reductase, which controls the mevalonate pathway for ergosterol formation to induce lipid accumulation. This lipid isolation from yeast cell was improved using green solvent viz. liquid-CO2. This liquid-CO2 extract was enriched with unsaturated lipid (46.96%) including ω-fatty acids such as linoleic (17.61%) and linolenic (5.35%). Thus, the SCO is produced using food waste as the source of carbon as well as an inhibitor, and this lipid is treated as natural to find suitable for nutritional purposes. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a dietary polyphenol that widely exists in grapes, strawberries, and walnuts. It usually exerts multiple biological activities together with its in vivo metabolites called urolithins. EA and urolithins had been proposed as natural agents for applying on the early intervention of Alzheimer’s disease (AD). However, the neuroprotective effects of those small molecules have not been confirmed, and the action mechanism is not clear. Deposition of beta-amyloid (Aβ) protein is well documented as being involved in the initiation and pathological process of AD. In the present study, we investigated the attenuating effects of EA and several urolithins on Aβ25–35-induced neuronal injury and its underlying molecular mechanism by constructing the in vitro AD cell model of PC12 cells and primary neurons. The results revealed that EA and urolithins especially the UM5 and UM6 exerted promising neuroprotective effects in improving the Aβ25–35-induced cell damage and lactate dehydrogenase (LDH) leakage, reducing reactive oxygen species (ROS) production, inhibiting neuronal apoptosis, and promoting neurite outgrowth. These results provide new insights into the development of UM5 and UM6 as anti-AD candidates. A network pharmacology analysis combining molecular docking strategy was further adopted to predict the signaling pathway involved in the anti-AD action of EA and urolithins, and the activation of PI3K-Akt, as well as the inhibition of MAPK was found to be involved.

Carbon steel is one of the widely used metallic material, although its limited corrosion resistance. To improve its anti-corrosion performance, organic coatings such as epoxy have been an excellent option due to their barrier mechanism. Nevertheless, the elevated brittleness and porosity observed in this type of coating, coupled with the weak bonding interface between epoxy and carbon steel, significantly hampered their protective capabilities. The organofunctional silanes are candidates to be used as pre-treatment between epoxy coating and carbon steel interface because of their good corrosion resistance but as a limitation they can present small pores and microcracks. Therefore, the anticorrosive and mechanical properties of silane films can be adapted and further improved by strengthening the coatings through some modifications, such as the incorporation of green corrosion inhibitors into the film, reducing the access of aggressive species to the metal. In this context, the objective of this research is to evaluate the adhesion and anticorrosive properties of an epoxy-based organic coating pre-treated with a silane film obtained by tetraethoxysilane (TEOS) with γ-glycidoxypropyltrimethoxysilane (GPTMS) modified with the garlic peel powder as a corrosion inhibitor (Allium sativum L.). The investigation of the surface features as morphology and the corrosion resistance of the silane-epoxy coatings were studied by scanning electron microscope (SEM) and electrochemical characterization techniques, such as, electrochemical impedance spectroscopy (EIS), linear and potentiodynamic polarization. Also, the coating adherence was evaluated by pull-off tests. The results of the EIS showed that all samples coated with silane+ epoxy coating have better anticorrosion performance than the sample coated with just epoxy painting. Besides, SEM images showed that the silane film improved the cohesion between substrate and coating system, with the clear appearance of delamination in the system silane free. In general, the results of these different techniques indicate that the film modified with the natural inhibitor has improved anticorrosive properties compared to the film without silane or natural green inhibitors. [Display omitted] • Silane-based coating was used to improve the adhesion of an epoxy coating. • EIS proved that silane monolayer grinded + epoxy has high anticorrosion performance. • SEM showed that sol-gel added before epoxy coating increased the adherence of paint. • Pull-off proved the adhesion properties of epoxy applied to steel with pretreatment. [ABSTRACT FROM AUTHOR]

Undesired browning reaction catalyzed by polyphenol oxidase (PPO) has reduced the nutritional quality and customer acceptance of the products. The inhibitory effects of six coastal plants including Sonneratia alba, Rhizophora apiculata, Syzygium grande, Rhizophora mucronata, Hibiscus tiliaceus and Bruguiera gymnorhiza on PPO in banana, sweet potato and ginger were studied based on oxidation of pyrocatechol. Banana exhibited the highest PPO activity (141,600 U), followed by sweet potato (43,440 U) and ginger (26,880 U). Banana PPO was strongly inhibited by R. apiculata (70.87%) and sweet potato PPO was strongly inhibited by S. alba (82.00%). In general, most banana PPO was the most susceptible to inhibition with all inhibitors having inhibition higher than 60.00% at 0.5 mg/ml and ginger PPO was the least susceptible with all inhibitors showing less than 50.00% inhibition at 0.5 mg/ml. Coastal plant extracts are potentially to be developed as natural inhibitors for preventing enzymatic browning of fruits and vegetables. [ABSTRACT FROM AUTHOR]

To improve the processing quality of potatoes, phosphate buffer extract (PBE), 50% ethanol (E50), and aqueous extract (AE) of tartary buckwheat seedlings were evaluated for their ability to inhibit the enzymatic browning of potatoes. The results suggest that all extracts of tartary buckwheat seedlings exert significant inhibitory effects on the polyphenol oxidase (PPO) activity in potatoes. The relative concentrations required for a 50% reduction in the PPO activity (IC50) were 0.21, 0.28 and 0.41 mg mL−1, for PBE, E50 and AE, respectively. The strongest inhibitory activity was observed for PBE, followed by E50 and AE. Four flavone compounds in the PBE of tartary buckwheat seedlings (i.e., rutin, kaempferol-3-O-rutinoside, quercetin, and kaempferol) were identified by high-performance liquid chromatography. These compounds were subsequently evaluated for their roles in the inhibition of PPO from potatoes using a model system. The results indicated that rutin exhibited the highest inhibition rate on the PPO of potato. A synergistic inhibitory effect was observed by mixing rutin, kaempferol-3-O-rutinoside, quercetin, and proteins. The inhibitory patterns of rutin, kaempferol-3-O-rutinoside, and quercetin on the enzyme were noncompetitive and reversible, with inhibitory constants of 0.12, 0.31, and 0.40 mg mL−1, respectively. Flavonoids from tartary buckwheat seedlings may exhibit a common mechanism with phenolic compounds, involving the blockage of the reaction of oxygen with PPO leading to the inhibition of the enzymes involved in browning. Based on these results, extracts of tartary buckwheat seedlings can be used as potent natural inhibitors.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PLpro) and main protease (Mpro)/3-chymotrypsin-like protease (3CLpro). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PLpro and Mpro/3CLpro proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease.

The use of corrosion inhibitors is one of the most common methods to combat acid corrosion. The current studies aim to apply natural products as corrosion inhibitors, once the most used compounds are mostly toxic to the environment and to humans. The present paper purposes the application of an aqueous extract of agro-industrial waste (AEAW) to inhibit the corrosion of stainless steel AISI 304 in sulfuric acid. Gravimetric and electrochemical experiments were performed. The gravimetric experiments revealed that the extract acts as an inhibitor for stainless steel, showing inhibitory efficiency up to 81.6%. The electrochemical tests show that the AEAW makes the steel surface more noble. The extract acts by adsorption in the metallic surface, following a Temkin isotherm. The results indicate that the AEAW is a promising substitute of conventional organic compounds as a corrosion inhibitor to AISI 304 stainless steel in sulfuric acid.

Acetylcholinesterase (AChE) inhibition is the standard therapy method used for age related disorders. Alzheimer Disease (AD) is the most widespread age related disease, affecting over 20 million individuals around the globe. AD is characterized by senile plaquets and cholinergic deficits. Many drugs currently used for the treatment of AD have severe neuronal side effects. Therefore in this paper we have attempted to identify AChE inhibitor which is natural and has negligible side effects than conventional drugs used in AD treatment. With the development in the cholinergic neurotransmission studies, inhibition of AChE has emerged as the most promising strategy in AD treatment. Compounds which inhibit/delay the hydrolysis of acetylcholine by AChE are known as AChE inhibitors and such compound(s) could become a perfect drug candidate(s). In this study, we have focused on the virtual screening, precision based docking and molecular dynamics studies for the identification and validation of natural inhibitors of AChE. 251 natural inhibitors from plants were identified, screened and docked against the human AChE using Glide module of Schrödinger suites. After screening and docking a natural compound Diplacone showed the superior glide score of -11.49 kcal/mol along with good binding energy -57.17kJ/mol. After analyzing the stability by molecular dynamics simulation techniques, it is convinced that natural compound Diplacone could be a better drug candidate for AD rather than its already established allopathic counterparts. Further in-vitro and clinical studies investigation are required for the validation of these studies. [ABSTRACT FROM AUTHOR]

Thrombin is the key enzyme of the entire hemostatic process since it is able to exert both procoagulant and anticoagulant functions; therefore, it represents an attractive target for the developments of biomolecules with therapeutic potential. Thrombin can perform its many functional activities because of its ability to recognize a wide variety of substrates, inhibitors, and cofactors. These molecules frequently are bound to positively charged regions on the surface of protein called exosites. In this review, we carried out extensive analyses of the structural determinants of thrombin partnerships by surveying literature data as well as the structural content of the Protein Data Bank (PDB). In particular, we used the information collected on functional, natural, and synthetic molecular ligands to define the anatomy of the exosites and to quantify the interface area between thrombin and exosite ligands. In this framework, we reviewed in detail the specificity of thrombin binding to aptamers, a class of compounds with intriguing pharmaceutical properties. Although these compounds anchor to protein using conservative patterns on its surface, the present analysis highlights some interesting peculiarities. Moreover, the impact of thrombin binding aptamers in the elucidation of the cross-talk between the two distant exosites is illustrated. Collectively, the data and the work here reviewed may provide insights into the design of novel thrombin inhibitors.

The Citrus aurantifolia leaves extract was tested for corrosion inhibition on the mild steel in a 0.5 M sulfuric acid solution using weight loss, Tafel and EIS. The state of mixed adsorption with the potentiodynamic polarization effect is shown. Citrus aurantifolia showed the strongest corrosion inhibition of 96.46% at a concentration of 250 mg/L. SEM and AFM are used to verify the formation of a protective layer on the surface of mild steel. The adsorption phenomenon was verified using UV-Vis. spectroscopic technique, whereas FT-IR confirmed the presence of several functional groups containing heteroatoms. Adsorption of the inhibitory molecules on the mild steel surface followed the Langmuir adsorption isotherm. All obtained results ensure that C. aurantifolia leaves extract can form an effective blocking layer and control the corrosion process. [ABSTRACT FROM AUTHOR]

Crofton weed is a major invasive species in China. It exhibits superior growth characteristics and can outcompete with native species via allolepathic effects and modulation of the soil fungal microbiome. The simple removal of invading plants will not ensure restoration of the habitat due to the persistence of allelochemicals and viable seeds in the surrounding soil. An orthogonal experimental design was employed to evaluate the effects of three control factors (A, powdered natural inhibitor species to retard growth; B, activated charcoal to absorb allelochemicals; and C, fungicide to reduce fungal modulation effects), applied at three levels, on the growth and competitive ability of Crofton weed against two native species, in a pot‐culture experiment. All treatments reduced all measured growth parameters (P < 0.05) except for a specific leaf area, when compared with control plants. Furthermore, the competitive capacity of Crofton weed was decreased in the treatments while that of the native species was improved. Application to soil of the powdered natural inhibitor species and of activated charcoal significantly inhibited plant growth and competitive ability of Crofton weed (P < 0.05). Application of fungicide was less effective, but significantly reduced the specific leaf area of Crofton weed plants (P < 0.05). The specific combination of factors producing the greatest decrease in plant growth and competitive ability (compared with the control) included the addition of Delavaya toxocarpa powder (37.5 g per kg soil), addition of activated charcoal to soil at a ratio of 1:3 (v/v) (62.5 g per kg soil), and application of fungicide (Thiophanate‐Methyl) (0.28 g per kg soil). [ABSTRACT FROM AUTHOR]

Bitis arietans venom (BAV) can induce severe pathophysiological disorders after envenoming. However, studies have shown that the Moringa oleifera fraction is effective against BAV toxicities and contains bioactive compounds with significant antivenom potency. This research aimed to identify the main active antivenom compound in the M. oleifera fraction responsible for neutralizing the toxicities induced by BAV. The compounds identified from M. oleifera fraction were docked in silico against the catalytic site of the Snake Venom Metalloproteinase (SVMP) to determine the lead inhibitor compound. The antivenom potency of the lead inhibitor compound was tested against BAV toxicities and metalloproteinase isolated from BAV using in vitro and in vivo methods, while EchiTab-Plus polyvalent antivenom served as a standard drug. The in silico prediction revealed kaempferol as the lead inhibitor compound with a docking score of −7.0 kcal/mol. Kaempferol effectively inhibited metalloproteinase activity at 0.2 mg/ml, compared to antivenom (0.4 mg/ml) and demonstrated significant antihaemorrhagic, antihaemolytic and coagulant effects against BAV activities. Furthermore, kaempferol showed a significant dose-dependent effect on altered haematological indices observed in rats challenged with LD 50 of BAV. Envenomed rats also showed an increase in oxidative stress biomarkers and antioxidant enzyme activity in the heart and kidney. However, treatment with kaempferol significantly (P < 0.05) decreased malondialdehyde levels and SOD activity with concomitant enhancement of glutathione levels. Severe histopathological defects noticed in the organ tissues of envenomed rats were ameliorated after kaempferol treatment. Kaempferol is identified as the main active antivenom compound in M. oleifera , and this research highlights the potential of the compound as an effective alternative to snakebite treatment. [Display omitted] • In silico studies revealed kaempferol as the main inhibitor of SVMP. • Kaempferol abolished B. arietans metalloproteinase activity, • Significantly inhibited biological activities of the venom in vitro , • Modulated altered haematological indices including antioxidant enzyme activities and • Ameliorated histopathological defects noticed in organ tissues in vivo. [ABSTRACT FROM AUTHOR]

Bixin, the key pigment of Bixa orellana L., is an apo-carotenoid found in the seed arils. The present study aimed to quantitatively determine the bixin content of seeds and explore its anti-cancer activity through in silico studies. The bixin content from the seeds of the local genotype, TNMTP8, quantified by RP-HPLC was 4.58 mg per gram. The prediction of pharmacological activity suggested that bixin may serve as a BRAF, MMP9, TNF expression inhibitors, and TP53 expression enhancer. According to molecular docking analysis, bixin interacted with eight different skin cancer targets and had the lowest binding energy compared to the standard drug, 5-fluorouracil. The binding score between bixin and the targets ranged from -4.7 to -8.7 kcal/mol. The targets BRAF and SIRT3 interacted well with bixin, with binding energies as low as -8.3 and -8.7 kcal/mol, respectively. Hence, the dynamic behavior of these two docked complexes throughout a 500 ns trajectory run was investigated further. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) values, and total contacts as a function of time recorded during scrutiny suggest that both complexes were stable. This was validated by post-molecular dynamics analysis using Molecular Mechanics Generalized Born Surface Area (MM-GBSA). Principal component analysis (PCA) was used to analyze the significant differences in motion exhibited by BRAF-Bixin and SIRT3-Bixin. The results showed that bixin is a promising source for potential treatment interventions in skin cancer therapies.Communicated by Ramaswamy H. Sarma.

The ATP synthase is a ubiquitous nanomotor that fuels life by the synthesis of the chemical energy of ATP. In order to synthesize ATP, this enzyme is capable of rotating its central rotor in a reversible manner. In the clockwise (CW) direction, it functions as ATP synthase, while in counter clockwise (CCW) sense it functions as an proton pumping ATPase. In bacteria and mitochondria, there are two known canonical natural inhibitor proteins, namely the ε and IF1 subunits. These proteins regulate the CCW F1FO-ATPase activity by blocking γ subunit rotation at the αDP/βDP/γ subunit interface in the F1 domain. Recently, we discovered a unique natural F1-ATPase inhibitor in Paracoccus denitrificans and related α-proteobacteria denoted the ζ subunit. Here, we compare the functional and structural mechanisms of ε, IF1, and ζ, and using the current data in the field, it is evident that all three regulatory proteins interact with the αDP/βDP/γ interface of the F1-ATPase. In order to exert inhibition, IF1 and ζ contain an intrinsically disordered N-terminal protein region (IDPr) that folds into an α-helix when inserted in the αDP/βDP/γ interface. In this context, we revised here the mechanism and role of the ζ subunit as a unidirectional F-ATPase inhibitor blocking exclusively the CCW F1FO-ATPase rotation, without affecting the CW-F1FO-ATP synthase turnover. In summary, the ζ subunit has a mode of action similar to mitochondrial IF1, but in α-proteobacteria. The structural and functional implications of these intrinsically disordered ζ and IF1 inhibitors are discussed to shed light on the control mechanisms of the ATP synthase nanomotor from an evolutionary perspective. [ABSTRACT FROM AUTHOR]

Guar gum (GG) was investigated as a possible eco-friendly corrosion inhibitor for pure aluminium in a 1-M HCl solution at different temperatures and immersion times using gravimetric and electrochemical techniques. The results showed that GG was a good corrosion inhibitor for pure aluminium in the studied environment. The inhibition efficiency of GG increased with increasing inhibitor concentration and immersion time but decreased with increasing temperature. Polarisation measurements revealed that GG was a mixed type inhibitor with a higher influence on the cathodic reaction. The adsorption behaviour of the investigated inhibitor was found to obey the Temkin adsorption isotherm and the calculated values of the standard free adsorption energy indicate mixed-type adsorption, with the physical adsorption being more dominant. The associated activation energy (Ea) and the heat of adsorption (Qa) supported the physical adsorption nature of the inhibitor. Fourier-transform infrared spectroscopy (FTIR) and Raman/SERS were used to explain the adsorption interaction between the inhibitor with the surface of the metal. The results suggested that most inhibition action of GG is due to its adsorption of the metal surface via H-bond formation.

Phosphodiesterase-4 (PDE4) is an important drug target for treatment of inflammation-related diseases. Till now, natural PDE4 inhibitors are rare and their co-crystal structures with PDE4 are hardly available. In the present study, selaginpulvilins K and L ( 1 and 2 ), two novel fluorene derivatives, were isolated from a traditional Chinese medicine Selaginella pulvinata and exhibited remarkable inhibition against phosphodiesterase-4D (PDE4D) at IC 50 11 nM and 90 nM, respectively. Compound 1 also showed a good selectivity across PDE families with the selective fold ranging from 30 to 909. To understand the recognition mechanism of selaginpulvilins towards PDE4, the crystal structure of PDE4D bound with 1 was successfully determined by the X-ray diffraction method and presented an unusual binding mode in which the stretched skeleton of the inhibitor bound shallowly to the active site but had interactions with multi sub-pockets, such as Q, HC, M, and S, especially strong interaction with the metal region. Assisted with molecular modeling, the structure–activity relationship and the selectivity of selaginpulvilins were also well explored, which would facilitate the future rational inhibitor design or structural optimizations. [ABSTRACT FROM AUTHOR]

Plant-based medicine actually restores the balance in the body instead of treating the source of the disease. The strain of coronavirus (SAR-CoV-2) going to be more serious due to the lack of a reliable treatment option. Holistic treatment for this disease is in the form of Ayurveda as traditional medicine. As the infection of coronavirus is spreading like a wildfire, so the one way to fight is 'immunity'. Building immunity is the only way to stay safe and healthy and prepared themselves for the ongoing pandemic. In the current scenario, good immunity safeguard us from disease progression and prevention from this deadly virus. Giloy herb came into the limelight after the start of the COVID-19 pandemic due to its immunomodulatory and antiviral activity. The genome sequencing of Giloy is proved to be a breakthrough for controlling the COVID-19.Communicated by Ramaswamy H. Sarma.

Main protease (M pro ) is a critical enzyme in the life cycle of severe acute respiratory syndrome Coronavirus -2 (SARS-CoV-2). Due to its essential role in the maturation of the polyproteins, the necessity to inhibit M pro is one of the essential means to prevent the outbreak of COVID-19. In this context, this study was conducted on the natural compounds of medicinal plants that are commonly available in the Middle East to find out the most potent one to inhibit M pro with the best bioavailability and druglikeness properties. A total of 3392 compounds of sixty-six medicinal plants were retrieved from PubChem database and docked against M pro . Thirty compounds with the highest docking scores with M pro were chosen for further virtual screening. Variable druglikeness and toxicity potentials of these compounds were evaluated using SwissADME and Protox servers respectively. Out of these virtually screened compounds, artecanin was predicted to exhibit the most favourable druglikeness potentials, accompanied by no predicted hepatoxicity, carcinogenicity, mutagenicity, and cytotoxicity. Molecular dynamics (MD) simulations showed that M pro -artecanin complex exhibited comparable stability with that observed in the ligand-free M pro . This study revealed for the first time that artecanin from Laurus nobilis provided a novel static and dynamic inhibition for M pro with excellent safety, oral bioavailability, and pharmacokinetic profile. This study suggested the ability of artecanin to be used as a potential natural inhibitor that can be used to block or at least counteract the SARS-CoV-2 invasion.Communicated by Ramaswamy H. Sarma.

The structure of F1-ATPase from Saccharomyces cerevisiae inhibited by the yeast IF1 has been determined at 2.5 Å resolution. The inhibitory region of IF1 from residues 1 to 36 is entrapped between the C-terminal domains of the αDP- and βDP-subunits in one of the three catalytic interfaces of the enzyme. Although the structure of the inhibited complex is similar to that of the bovine-inhibited complex, there are significant differences between the structures of the inhibitors and their detailed interactions with F1-ATPase. However, the most significant difference is in the nucleotide occupancy of the catalytic βE-subunits. The nucleotide binding site in βE-subunit in the yeast complex contains an ADP molecule without an accompanying magnesium ion, whereas it is unoccupied in the bovine complex. Thus, the structure provides further evidence of sequential product release, with the phosphate and the magnesium ion released before the ADP molecule.

Ellagic acid (EA) is a dietary polyphenol that widely exists in grapes, strawberries, and walnuts. It usually exerts multiple biological activities together with its in vivo metabolites called urolithins. EA and urolithins had been proposed as natural agents for applying on the early intervention of Alzheimer's disease (AD). However, the neuroprotective effects of those small molecules have not been confirmed, and the action mechanism is not clear. Deposition of beta-amyloid (Aβ) protein is well documented as being involved in the initiation and pathological process of AD. In the present study, we investigated the attenuating effects of EA and several urolithins on Aβ 25-35 -induced neuronal injury and its underlying molecular mechanism by constructing the in vitro AD cell model of PC12 cells and primary neurons. The results revealed that EA and urolithins especially the UM5 and UM6 exerted promising neuroprotective effects in improving the Aβ 25-35 -induced cell damage and lactate dehydrogenase (LDH) leakage, reducing reactive oxygen species (ROS) production, inhibiting neuronal apoptosis, and promoting neurite outgrowth. These results provide new insights into the development of UM5 and UM6 as anti-AD candidates. A network pharmacology analysis combining molecular docking strategy was further adopted to predict the signaling pathway involved in the anti-AD action of EA and urolithins, and the activation of PI3K-Akt, as well as the inhibition of MAPK was found to be involved., Competing Interests: W-ZH was employed by Guangdong Luofushan Sinopharm Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhang, Ren, Zhou, Zhou, Huang, Piao, Yang, Wang and Ge.)

This study was conducted to identify false-positive outcomes and drug residues in milk samples over withdrawal times and to determine whether the positive results were caused by drug residues or natural inhibitors. A total of 73 milk samples over withdrawal times after the last intramammary infusion were collected from each treated quarter of cows and tested using the Delvotest SP assay. Reading time was 150, 165, and 180 min, and results of samples were recorded according to the color of the well containing the control milk sample. There were 24, 20, and 12 positive samples at the reading times of 150, 165, and 180 min, respectively. All 24 positive milk samples were heated at 82°C for 5 min and retested to verify that the positive results were caused by drug residues or natural inhibitors. Twenty-one samples that exhibited positive results were negative after heat treatment, and drug residues were not identified by LacTek and Charm tests. However, 3 samples that exhibited positive results from heat treatment of 82°C were positive for drugs. In our study, most positive results (89%) in the milk samples over withdrawal times were false-positive results by natural inhibitors. Moreover, the heat treatment is a fast, simple, and inexpensive method to remove false-positive results and has no effect on positive samples containing drugs. We suggest that heat treatment before screening tests is an effective way to reduce false-positive results in the milk samples. [ABSTRACT FROM AUTHOR]

Arg-gingipain (Rgp) is a major cysteine proteinase produced by the oral bacterium Porphyromonas gingivalis, which is a major pathogen of advanced periodontal diseases. This enzyme is important for the bacterium both to exhibit its virulence and to survive in periodontal pockets. The development of Rgp inhibitors thus provides new therapeutic approaches to periodontal diseases. In this study, we first isolated and purified a novel and potent inhibitor of Rgp from the culture supernatant of Streptomyces species strain FA-70, now designated as FA-70C1. This compound was found to be an antipain analog composed of phenylalanyl-ureido-citrullinyl-valinyl-cycloarginal (C[sub27]H[sub43]N[sub9]O[sub7]). The K[subi] value was calculated to be 4.5x10[sup-9] M when benzyloxycarbonyl-phenylalanylarginine-4-methly-coumaryl-7-amide was used as a substrate. This compound also inhibited cathepsins B, L, and H, though their K[subi] values were much higher than that of Rgp. FA-70C1 had little or no inhibitory activity on Lys-gingipain, another cysteine proteinase of P. gingivalis. The Rgp-induced degradation of various human proteins was completely blocked by this inhibitor. Disruption of both the bactericidal activity of polymorphonuclear leukocytes and the viability of human fibroblasts and umbilical vein endothelial cells induced by the culture supernatant of P. gingivalis was suppressed by the inhibitor in a dose-dependent manner. The enhancement of vascular permeability induced by in vivo administration of the culture supernatant of P. gingivalis was strongly inhibited by the inhibitor. Furthermore, the growth of P. gingivalis was suppressed by FA-70C1 in a dose-dependent manner. These results strongly suggest that FA-70C1 is a useful tool to prevent the virulence of P. gingivalis. [ABSTRACT FROM AUTHOR]

In this study we examined surface expression of CD26 and the corresponding enzyme activity of dipeptidyl peptidase IV (DPPIV) on the cells of immature murine T-cell line, R1.1. The data obtained have shown that R1.1 cells express high density of surface CD26 as compared to normal thymus cells. This was associated with strong enzyme activity, which, based on substrates and inhibitor specificity, corresponded to DPPIV. The DPPIV enzyme activity of R1.1 cells was 10 times stronger than that found on normal murine thymus cells (Vmax = 39 μmol/min/106 cells, vs 3.7 μmol/min/106 cells, respectively). Upon activation with anti-CD3, up-regulation of both membrane CD26, as well as of DPPIV enzyme activity on R1.1 cells were observed. The finding of strong DPPIV on R1.1 cells makes them suitable model for testing putative substrates/inhibitors of the enzyme in its natural microenvironment. Since in addition to strong DPPIV, R1.1 cells also express kappa opioid receptors (KOR) [European Journal of Pharmacology 227 (1992) 257], we tested the effect of dynorphin-A(1–17), an endogenous opioid peptide with KOR selectivity, on DPPIV of R1.1 cells. Dynorphin-A(1–17) down-regulated DPPIV in a dose-dependent manner, with the potency similar to that of substance P, a known natural DPPIV substrate [Journal of Pharmacology and Experimental Therapeutics 260 (1992) 1257]. DPPIV down-regulation was resistant to bestatin and thiorphan, the inhibitors of two cell surface peptidases (APN and NEP, respectively) with potential of dynorphin-A(1–17) degradation, suggesting that the mechanism underlying the observed effect does not involve degradative products of dynorphin-A(1–17). DPPIV down-regulation was also resistent to KOR antagonist, NBI, suggesting that the mechanism underlying the observed phenomenon involves neither cointernalization of KOR and DPPIV. Collectively, cells of immature T cell line, R1.1 exert strong DPPIV enzyme activity, which could be down-regulated in the presence of dynorphin-A(1–17) by mechanism that presumably includes non-substrate inhibition. By down-regulating DPPIV, dynorphin-A(1–17) may indirectly affect activity and/or specificity of natural substrates of DPPIV, such as substance P, RANTES, and endomorphins. [Copyright &y& Elsevier]