An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable and integral role in the maturation and replication of the MERS-CoV virus, the 3C-like protease is unavoidly a viable therapeutic target. In this study, 2369 phytoconstituents were enlisted from Japanese medicinal plants, and these compounds were screened against 3C-like protease to identify feasible inhibitors. The best three compounds were identified as Kihadanin B, Robustaflavone, and 3-beta-O- (trans-p-Coumaroyl) maslinic acid, with binding energies of -9.8, -9.4, and -9.2 kcal/mol, respectively. The top three potential candidates interacted with several active site residues in the targeted protein, including Cys145, Met168, Glu169, Ala171, and Gln192. The best three compounds were assessed by in silico technique to determine their drug-likeness properties, and they exhibited the least harmful features and the greatest drug-like qualities. Various descriptors, such as solvent-accessible surface area, root-mean-square fluctuation, root-mean-square deviation, hydrogen bond, and radius of gyration, validated the stability and firmness of the protein-ligand complexes throughout the 100ns molecular dynamics simulation. Moreover, the top three compounds exhibited better binding energy along with better stability and firmness than the inhibitor (Nafamostat), which was further confirmed by the binding free energy calculation. Therefore, this computational investigation could aid in the development of efficient therapeutics for life-threatening MERS-CoV infections.

Hydrogen-rich water: a key player in boosting wheat (Triticum aestivum L.) seedling growth and drought resilience.

In the modern world, wheat, a vital global cereal and the second most consumed, is vulnerable to climate change impacts. These include erratic rainfall and extreme temperatures, endangering global food security. Research on hydrogen-rich water (HRW) has gained momentum in plant and agricultural sciences due to its diverse functions. This study examined the effects of different HRW treatment durations on wheat, revealing that the 4-h treatment had the highest germination rate, enhancing potential, vigor, and germination indexes. This treatment also boosted relative water content, root and shoot weight, and average lengths. Moreover, the 4-h HRW treatment resulted in the highest chlorophyll and soluble protein concentrations in seeds while reducing cell death. The 4-h and 5-h HRW treatments significantly increased H2O2 levels, with the highest NO detected in both root and shoot after 4-h HRW exposure. Additionally, HRW-treated seeds exhibited increased Zn and Fe concentrations, along with antioxidant enzyme activities (CAT, SOD, APX) in roots and shoots. These findings suggest that HRW treatment could enhance wheat seed germination, growth, and nutrient absorption, thereby increasing agricultural productivity. Molecular analysis indicated significant upregulation of the Dreb1 gene with a 4-h HRW treatment. Thus, it shows promise in addressing climate change effects on wheat production. Therefore, HRW treatment could be a hopeful strategy for enhancing wheat plant drought tolerance, requiring further investigation (field experiments) to validate its impact on plant growth and drought stress mitigation.

Effects of gamma-radiation on microbial, nutritional, and functional properties of Katimon mango peels: A combined biochemical and in silico studies.

Gamma radiation has notable impacts on the flesh of mangoes. In this research, Katimon mangoes were subjected to different levels of irradiation (0.5, 1.0, 1.5, and 2.0 kGy) using a60Co irradiator. The results showed that irradiation significantly reduced the microbial population in the mango peels, with the 1.5 kGy dose showing the most significant reduction. Irradiation also delayed ripening and extended the shelf life of the mango peels. The total fat, protein, ash, moisture, and sugar content of the mango peels were all affected by irradiation. The total protein content, ash content and moisture content increased after irradiation, while the fat content remained relatively unchanged. The sugar content increased in all samples after storage, but the non-irradiated samples had higher sugar levels than the irradiated ones. The dietary fiber content of the mango peels was not significantly affected by irradiation. The vitamin C content decreased in all samples after storage. The titratable acidity and total soluble solids content of the mango peels increased after storage, but there were no significant differences between the irradiated and non-irradiated samples. Antioxidant activity and cytotoxicity assessment highlighted the antioxidant potential and reduced toxicity of irradiated samples. Additionally, the antimicrobial effectiveness of irradiated mango peels was evaluated. The most substantial inhibitory zones (measuring 16.90 ± 0.35) against Pseudomonas sp. were observed at a radiation dose of 1.5 kGy with 150 µg/disc. To identify potential antimicrobial agents, the volatile components of mangoes irradiated with 1.5 kGy were analyzed through GC-MS. Subsequently, these compounds were subjected to in silico studies against a viable protein, TgpA, of Pseudomonas sp. (PDB ID: 6G49). Based on molecular dynamic simulations and ADMET properties, (-)-Carvone (-6.2), p-Cymene (-6.1), and Acetic acid phenylmethyl ester (-6.1) were identified as promising compounds for controlling Pseudomonas sp.

Antioxidant, Cytotoxicity, Antimicrobial Activity, and In Silico Analysis of the Methanolic Leaf and Flower Extracts of Clitoria ternatea.

Infectious diseases pose a significant threat to human health worldwide. To address this challenge, we conducted a comprehensive study on the leaf and flower extracts of Clitoria ternatea plants. Our research encompassed in vitro assessments of their antibacterial, antibiofilm, antioxidant, and cytotoxic properties. Additionally, we employed in silico screening to identify promising compounds with potential applications in developing novel anti-Escherichia coli medications. Notably, our investigation revealed a remarkable inhibition zone of 13.00 ± 1 mm when applying the leaf extract (200 µg/ml) against E. coli, showcasing its potent antibacterial properties. Furthermore, both the leaf and flower extracts exhibited substantial biofilm inhibition efficacy against S. aureus, with inhibition percentages of 54% and 58%, respectively. In the realm of antioxidant activity, the leaf and flower extracts of C. ternatea displayed noteworthy DPPH free radical scavenging capabilities. Specifically, the leaf extract exhibited a substantial activity of 62.39% at a concentration of 150 µg/ml, while the flower extract achieved 44.08% at the same concentration. Our study also evaluated the impact on brine shrimp, where the floral extract displayed a significantly higher mortality rate of 93.33% at a dosage of 200 µg/ml compared to the leaf extract. To elucidate potential therapeutic targets, we utilized molecular docking techniques, focusing on the acbR protein (5ENR) associated with antibiotic resistance in E. coli. In this analysis, compounds isolated from the C. ternatea leaf extract, namely D1 (CID-14478556), D2 (CID-6423376), and D3 (CID-20393), exhibited binding energies of -8.2 kcal/mol, -6.5 kcal/mol, and -6.3 kcal/mol, respectively. Additionally, compounds from the flower extract, E1 (CID-5282761), E2 (CID-538757), and E3 (CID-536762), displayed binding energies of -5.4 kcal/mol, -5.3 kcal/mol, and -5.1 kcal/mol, respectively. In conclusion, the leaf and flower extracts derived from C. ternatea represent a promising natural resource with potential therapeutic applications in combating antibiotic-resistant pathogens.

Probiotic potential of Lactobacillus plantarum DMR14 for preserving and extending shelf life of fruits and fruit juice.

The harmful effects of chemical preservatives are driving the need for natural ones. To meet this demand, probiotic lactic acid bacteria (LAB) were isolated from fermented oats in this study. The goals of this study were to separate and identify probiotic LAB from fermented oats, to determine how effective these LAB are at combating pathogenic microorganisms in vitro, and to investigate their preservative capacity by applying the bacterium's cell-free supernatant (CFS) to specific fruits and fruit juice. The isolated strain was identified as Lactobacillus plantarum DMR14 using morphological, biochemical, and molecular investigation. Antimicrobial, antibiofilm, anti-oxidant, pH tolerance, and antibiotic resistance assays were used to evaluate the strain's probiotic potential, showing that Lactobacillus plantarum DMR14 had the strongest antagonistic and anti-biofilm capacity against Shigella boydii. Furthermore, the bacteriocin-containing compounds, cell-free supernatant (CFS) of the LAB, were tested against three fruits and one fruit juice, with the cell-free supernatant (CFS) of the bacterium lengthening the shelf life of the fruits compared to the untreated ones. Furthermore, while the concentration of coliform bacteria decreased in the treated sugarcane juice, an increase in the concentration of lactic acid bacteria suggested that the strain may be used as a fruit preservative in food industries.

Klebsiella pneumoniae Volatile Organic Compounds (VOCs) Protect Artemia salina from Fish Pathogen Aeromonas sp.: A Combined In Vitro, In Vivo, and In Silico Approach.

Antibiotic resistance is an alarming threat all over the world, and the biofilm formation efficacy of bacteria is making the situation worse. The antagonistic efficacy of Klebsiella pneumoniae against one of the known fish pathogens, Aeromonas sp., is examined in this study. Moreover, Aeromonas sp.'s biofilm formation ability and in vivo pathogenicity on Artemia salina are also justified here. Firstly, six selected bacterial strains were used to obtain antimicrobial compounds against this pathogenic strain. Among those, Klebsiella pneumoniae, another pathogenic bacterium, surprisingly demonstrated remarkable antagonistic activity against Aeromonas sp. in both in vitro and in vivo assays. The biofilm distrusting potentiality of Klebsiella pneumoniae's cell-free supernatants (CFSs) was likewise found to be around 56%. Furthermore, the volatile compounds of Klebsiella pneumoniae were identified by GC-MS in order to explore compounds with antibacterial efficacy against Aeromonas sp. through an in silico study, where 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) (PDB: 5B7P) was chosen as a target protein for its unique characteristics and pathogenicity. Several volatile compounds, such as oxime- methoxy-phenyl-, fluoren-9-ol, 3,6-dimethoxy-9-(2-phenylethynyl)-, and 2H-indol-2-one, 1,3-dihydro- showed a strong binding affinity, with free energy of -6.7, -7.1, and -6.4 Kcal/mol, respectively, in complexes with the protein MTAN. Moreover, the root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, Klebsiella pneumoniae and its potential compounds can be employed as an alternative to antibiotics for aquaculture, demonstrating their effectiveness in suppressing Aeromonas sp.

Volatile compounds of Bacillus pseudomycoides induce growth and drought tolerance in wheat (Triticum aestivum L.).

The plant growth-boosting biofilm-forming bacteria Bacillus pseudomycoides is able to promote growth and drought stress tolerance in wheat by suppressing the MYB gene, which synthesizes Myb protein (TaMpc1-D4) through secreted volatile compounds. In the present study, Triticum aestivum seeds were inoculated with five distinct bacterial strains. The growth, germination rate, root-shoot length, RWC, and chlorophyll content of seedlings were investigated. Furthermore, the levels of soluble sugars, proteins, H2O2, NO, cell death, and antioxidant enzymes (CAT, SOD, POD, and APX) were observed throughout the growth stage. All of the results showed that B. pseudomycoides had a substantially higher ability to form biofilm and promote these traits than the other strains. In terms of molecular gene expression, B. pseudomycoides inoculation strongly expressed the Dreb1 gene by silencing the expression of MYB gene through secreted volatile compounds. For identifying the specific volatile compound that silenced the MYB gene, molecular docking with Myb protein was performed. Out of 45 volatile compounds found, 2,6-ditert-butylcyclohexa-2,5-diene-1,4-dione and 3,5-ditert-butylphenol had a binding free energy of - 6.2 and - 6.5, Kcal/mol, respectively, which predicted that these compounds could suppress this protein's expression. In molecular dynamics simulations, the RMSD, SASA, Rg, RMSF, and hydrogen bonding values found assured the docked complexes' binding stability. These findings suggest that these targeted compounds may be suppressing Myb protein expression as well as the expression of Dreb1 and other drought response genes in wheat. More research (field trial) into plant growth and drought stress is needed to support the findings of this study.

Cell-Free Supernatants (CFSs) from the Culture of Bacillus subtilis Inhibit Pseudomonas sp. Biofilm Formation.

Biofilm inhibition has been identified as a novel drug target for the development of broad-spectrum antibiotics to combat infections caused by drug-resistant bacteria. Although several plant-based compounds have been reported to have anti-biofilm properties, research on the anti-biofilm properties of bacterial bioactive compounds has been sparse. In this study, the efficacy of compounds from a cell-free supernatant of Bacillus subtilis against a biofilm formation of Pseudomonas sp. was studied through in vitro, in vivo and in silico studies. Here, in well diffusion method, Bacillus subtilis demonstrated antibacterial activity, and more than 50% biofilm inhibition activity against Pseudomonas sp. was exhibited through in vitro studies. Moreover, molecular docking and molecular dynamics (MD) simulation gave insights into the possible mode of action of the bacterial volatile compounds identified through GC-MS to inhibit the biofilm-formation protein (PDB ID: 7M1M) of Pseudomonas sp. The binding energy revealed from docking studies ranged from -2.3 to -7.0 kcal mol-1. Moreover, 1-(9H-Fluoren-2-yl)-2-(1-phenyl-1H-ttetrazole5-ylsulfanyl)-ethanone was found to be the best-docked compound through ADMET and pharmacokinetic properties. Furthermore, MD simulations further supported the in vitro studies and formed a stable complex with the tested protein. Thus, this study gives an insight into the development of new antibiotics to combat multi-drug-resistant bacteria.

Biological Efficacy of Compounds from Stingless Honey and Sting Honey against Two Pathogenic Bacteria: An In Vitro and In Silico Study.

Honey inhibits bacterial growth due to the high sugar concentration, hydrogen peroxide generation, and proteinaceous compounds present in it. In this study, the antibacterial activity of stingless and sting honey against foodborne pathogenic bacteria isolated from spoiled milk samples was examined. The isolated bacterial strains were confirmed as Bacillus cereus and Listeriamonocytogenes through morphological, biochemical, and 16 s RNA analysis. Physiochemical characterizations of the honey samples revealed that both of the honey samples had an acidic pH, low water content, moderate reducing sugar content, and higher proline content. Through the disc diffusion method, the antibacterial activities of the samples were assayed and better results were observed for the 50 mg/disc honey. Both stingless and sting honey showed the most positive efficacy against Bacillus cereus. Therefore, an in silico study was conducted against this bacterium with some common compounds of honey. From several retrieved constituents of stingless and sting honey, 2,4-dihydroxy-2,5-dimethyl 3(2H)-furan-3-one (furan) and 4H-pyran-4-one,2,3-dihydro of both samples and beta.-D-glucopyranose from the stingless revealed high ligand-protein binding efficiencies for the target protein (6d5z, hemolysin II). The root-mean-square deviation, solvent-accessible surface area, the radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation and confirmed their stability. The combined effort of wet and dry lab-based work support, to some extent, that the antimicrobial properties of honey have great potential for application in medicine as well as in the food industries.

Plant-derived compounds effectively inhibit the main protease of SARS-CoV-2: An in silico approach.

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep literature mining and explored their potential to bind with and inhibit the main protease of SARS-CoV-2. The three most effective phytochemicals Cosmosiine, Pelargonidin-3-O-glucoside, and Cleomiscosin A had binding energies of -8.4, -8.4, and -8.2 kcal/mol, respectively, in the docking analysis. These molecules could bind to Gln189, Glu166, Cys145, His41, and Met165 residues on the active site of the targeted protein, leading to specific inhibition. The pharmacological characteristics and toxicity of these compounds, examined using absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses, revealed no carcinogenicity or toxicity. Furthermore, the complexes were simulated with molecular dynamics for 100 ns to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen profiles from the simulation trajectories. Our analysis validated the rigidity of the docked protein-ligand. Taken together, our computational study findings might help develop potential drugs to combat the main protease of the SARS-CoV-2 and help alleviate the severity of the pandemic.

The Emergence of SARS-CoV-2 Variants With a Lower Antibody Response: A Genomic and Clinical Perspective.

The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs.

Rolling back human pluripotent stem cells to an eight-cell embryo-like stage.

After fertilization, the quiescent zygote experiences a burst of genome activation that initiates a short-lived totipotent state. Understanding the process of totipotency in human cells would have broad applications. However, in contrast to in mice1,2, demonstration of the time of zygotic genome activation or the eight-cell (8C) stage in in vitro cultured human cells has not yet been reported, and the study of embryos is limited by ethical and practical considerations. Here we describe a transgene-free, rapid and controllable method for producing 8C-like cells (8CLCs) from human pluripotent stem cells. Single-cell analysis identified key molecular events and gene networks associated with this conversion. Loss-of-function experiments identified fundamental roles for DPPA3, a master regulator of DNA methylation in oocytes3, and TPRX1, a eutherian totipotent cell homeobox (ETCHbox) family transcription factor that is absent in mice4. DPPA3 induces DNA demethylation throughout the 8CLC conversion process, whereas TPRX1 is a key executor of 8CLC gene networks. We further demonstrate that 8CLCs can produce embryonic and extraembryonic lineages in vitro or in vivo in the form of blastoids5 and complex teratomas. Our approach provides a resource to uncover the molecular process of early human embryogenesis.

phytochemdb: a platform for virtual screening and computer-aided drug designing.

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed 'phytochemdb', a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood-Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. 'phytochemdb' is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. 'phytochemdb' is available for free at https://phytochemdb.com/.

Biochemical and Molecular Dynamics Study of a Novel GH 43 α-l-Arabinofuranosidase/ß-Xylosidase From Caldicellulosiruptor saccharolyticus DSM8903.

The complete hydrolysis of xylan can be facilitated by the coordinated action of xylanase and other de-branching enzymes. Here, a GH43 α-l-arabinofuranosidase/ß-xylosidase (CAX43) from Caldicellulosiruptor saccharolyticus was cloned, sequenced, and biochemically investigated. The interaction of the enzyme with various substrates was also studied. With a half-life of 120 h at 70°C, the produced protein performed maximum activity at pH 6.0 and 70°C. The enzyme demonstrated a higher activity (271.062 ± 4.83 U/mg) against para nitrophenol (pNP) α-L-arabinofuranosides. With xylanase (XynA), the enzyme had a higher degree of synergy (2.30) in a molar ratio of 10:10 (nM). The interaction of the enzyme with three substrates, pNP α-L-arabinofuranosides, pNP ß-D-xylopyranosides, and sugar beet arabinan, was investigated using protein modeling, molecular docking, and molecular dynamics (MD) simulation. During the simulation time, the root mean square deviation (RMSD) of the enzyme was below 2.5 Å, demonstrating structural stability. Six, five, and seven binding-interacting residues were confirmed against pNP α-L-arabinofuranosides, pNP ß-D-xylopyranosides, and arabinan, respectively, in molecular docking experiments. This biochemical and in silico study gives a new window for understanding the GH43 family's structural stability and substrate recognition, potentially leading to biological insights and rational enzyme engineering for a new generation of enzymes that perform better and have greater biorefinery utilization.

Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.

The spread of the Dengue virus over the world, as well as multiple outbreaks of different serotypes, has resulted in a large number of deaths and a medical emergency, as no viable medications to treat Dengue virus patients have yet been found. In this paper, we provide an in silico virtual screening and molecular dynamics-based analysis to uncover efficient Dengue infection inhibitors. Based on a Google search and literature mining, a large phytochemical library was generated and employed as ligand molecules. In this investigation, the protein target NS2B/NS3 from Dengue was employed, and around 27 compounds were evaluated in a docking study. Phellodendroside (-63 kcal/mole), quercimeritrin (-59.5 kcal/mole), and quercetin-7-O-rutinoside (-54.1 kcal/mole) were chosen based on their binding free energy in MM-GBSA. The tested compounds generated numerous interactions at Lys74, Asn152, and Gln167 residues in the active regions of NS2B/NS3, which is needed for the protein's inhibition. As a result, the stable mode of docked complexes is defined by various descriptors from molecular dynamics simulations, such as RMSD, SASA, Rg, RMSF, and hydrogen bond. The pharmacological properties of the compounds were also investigated, and no toxicity was found in computational ADMET properties calculations. As a result, this computational analysis may aid fellow researchers in developing innovative Dengue virus inhibitors.

Computational screening and biochemical analysis of Pistacia integerrima and Pandanus odorifer plants to find effective inhibitors against Receptor-Binding domain (RBD) of the spike protein of SARS-Cov-2.

Although World Health Organization-approved emergency vaccines are available in many countries, the mortality rate from COVID-19 remains high due to the fourth or fifth wave and the delta variant of the coronavirus. Thus, an effective mechanistic investigation in treating this disease is urgently needed. In this work, we extracted phytochemicals from two mangrove plants, Pistacia integerrima and Pandanus odorifer, assessing their potential actions against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. The antioxidant activities of Pistacia integerrima leaves and fruits were 142.10 and 97.13 µg/mL, respectively, whereas Pandanus odorifer leaves and fruits were 112.50 and 292.71 µg/mL, respectively. Furthermore, leaf extracts from both plants had lower cytotoxicity against Artemia salina than fruit extracts. Gas chromatography-mass spectrometry analysis revealed a total of 145 potential phytochemicals from these extracts. Three phytochemicals, 28-demethyl-beta-amyrone, 24-Noroleana-3,12-diene, and stigmasterol, displayed binding free energy values of - 8.3, -7.5, and - 8.1 Kcal/mol, respectively, in complexes with the spike protein of SARS-CoV-2. The root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, wet-lab validations are necessary to support these findings.

Antiviral peptides against the main protease of SARS-CoV-2: A molecular docking and dynamics study.

The recent coronavirus outbreak has changed the world's economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the ability to inhibit the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using multiple combinatorial docking programs, including PatchDock, FireDock, and ClusPro. The four best peptides, DRAMP00877, DRAMP02333, DRAMP02669, and DRAMP03804, had binding energies of -1125.3, -1084.5, -1005.2, and -924.2 Kcal/mol, respectively, as determined using ClusPro, and binding energies of -55.37, -50.96, -49.25, -54.81 Kcal/mol, respectively, as determined using FireDock, which were better binding energy values than observed for other peptide molecules. These peptides were found to bind with the active cavity of the SARS-CoV-2 main protease; at Glu166, Cys145, Asn142, Phe140, and Met165, in addition to the substrate-binding sites, Domain 2 and Domain 3, whereas fewer interactions were observed with Domain 1. The docking studies were further confirmed by a molecular dynamics simulation study, in which several descriptors, including the root-mean-square difference (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and hydrogen bond formation, confirmed the stable nature of the peptide-main protease complexes. Toxicity and allergenicity studies confirmed the non-allergenic nature of the peptides. This present study suggests that these identified antiviral peptide molecules might inhibit the main protease of SARS-CoV-2, although further wet-lab experiments remain necessary to verify these findings.

Fermentation optimization of cellulase production from sugarcane bagasse by Bacillus pseudomycoides and molecular modeling study of cellulase.

Degradation of cellulosic carbon, the most important natural carbon reservoirs on this planet by cellulase is very essential for valuable soluble sugars. This cellulase has potential biotechnological applications in many industrial sectors. Thus the demand of cellulase is increasing more frequently than ever. Agro industrial byproducts and suitable microbes are of an important source for the production of cellulase. Bacillus pseudomycoides and sugarcane bagasse were used for the production of cellulase and different process parameters influencing the production of cellulase were optimized here. The bacterium showed maximum cellulase production in the presence of sugarcane bagasse, peptone and magnesium sulfate at pH 7, 40 °C in 72 h of incubation. Primary structures of the cellulase is consists of 400 amino acid residues having molecular weight 44,790 Dalton and the theoretical PI is 9.11. Physiochemical properties of cellulase indicated that the protein has instability index 25.77. Seven hydrogen bonds were observed at multiple sites of the cellulase enzyme; His269, Asp237, Asn235, Tyr271, Ser272, Gln309, Asn233. This protein structure may play first hand in further development of exploring cellulase and cellulose interaction dynamics in Bacillus sp. Thus this bacterium may be useful in various industrial applications owing to its cellulase producing capability.

Biochemical and in silico study of leaf and bark extracts from Aphanamixis polystachya against common pathogenic bacteria.

Aphanamixis polystachya may be a natural, renewable resource against antibiotic-resistant bacterial infections. The antibacterial activity of A. polystachya leaf and bark extracts was investigated against three antibiotic-resistant bacterial species and one fungus. Methanolic leaf extract showed only limited antibacterial activity but both methanolic and aqueous bark extract showed high antimicrobial activity. In an antioxidant activity test, leaf and bark extracts exhibited 50% free radical scavenging at a concentration of 107.14 ± 3.14 µg/mL and 97.13 ± 3.05 µg/mL, respectively, indicating that bark extracts offer more antioxidative activity than leaf extracts. Bark extracts also showed lower toxicity than leaf extracts. This suggests that bark extracts may offer greater development potential than leaf extracts. The molecular dynamics were also investigated through the simulated exploration of multiple potential interactions to understand the interaction dynamics (root-mean-square deviation, solvent-accessible surface area, radius of gyration, and the hydrogen bonding of chosen compounds to protein targets) and possible mechanisms of inhibition. This molecular modeling of compounds derived from A. polystachya revealed that inhibition may occur by binding to the active sites of the target proteins of the tested bacterial strains. A. polystachya bark extract may be used as a natural source of drugs to control antibiotic-resistant bacteria.

Molecular docking and dynamics study to explore phytochemical ligand molecules against the main protease of SARS-CoV-2 from extensive phytochemical datasets.

BACKGROUND: The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world's economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (Mpro) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level. METHODS: In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the Mpro of SARS-CoV-2. RESULTS: The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of -8.9, -8.9, -8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories. CONCLUSIONS: Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.