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At a concentration of 4 g/L, an enteric polymer is utilized to target drug release in the small intestine and causes considerable toxicity in cells. Our ecology and ecosystem are also harmed by their non-biodegradable qualities. We isolated and identified polymer-degrading bacteria from industrial effluent in this work. The isolated strain's morphological, biochemical, and antibiotic sensitivities were also examined. The isolated strain was found to be gram-negative, round-shaped, and non-motile in morphological tests, while biochemical tests revealed it to be negative in starch agar and TSI but positive in methyl red, mannitol salt, Simmon citrate, urea agar, and catalase test. The isolated strain was highly resistant to ciprofloxacin and vancomycin. The isolated bacterium was identified as Acinetobacter sp. by 16S rRNA sequencing. Additionally, Acinetobacter sp. strains of Escherichia coli and Brevibacillus sp. were used separately to observe the degradation of five synthesized non-biodegradable polymers (maleic acid propane-1,2 diol glycerol co-polyester, maleic acid phthalic acid propane-1,2 diol glycerol co-polyester, maleic acid phthalic acid butan-1,4 diol glycerol co-polyester, phthalic acid succinic acid propane-1,2 diol glycerol co-polyester, and phthalic acid succinic acid buten-1,4 diol glycerol co-polyester. The capacity of all three strains to degrade the above-mentioned polymers was greater than 75%. E. coli, for example, had a rapid disintegration rate but was responsible for human gastrointestinal and urinary tract infections. As a result, our isolated Acinetobacter sp. can be employed to degrade synthetic polymers. [ J Adv Biotechnol Exp Ther 2022; 5(3.000): 487-496]

Marburg virus (MARV) has been a major concern since 1967, with two major outbreaks occurring in 1998 and 2004. Infection from MARV results in severe hemorrhagic fever, causing organ dysfunction and death. Exposure to fruit bats in caves and mines, and human-to-human transmission had major roles in the amplification of MARV outbreaks in African countries. The high fatality rate of up to 90% demands the broad study of MARV diseases (MVD) that correspond with MARV infection. Since large outbreaks are rare for MARV, clinical investigations are often inadequate for providing the substantial data necessary to determine the treatment of MARV disease. Therefore, an overall review may contribute to minimizing the limitations associated with future medical research and improve the clinical management of MVD. In this review, we sought to analyze and amalgamate significant information regarding MARV disease epidemics, pathophysiology, and management approaches to provide a better understanding of this deadly virus and the associated infection.

Abstract 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.

Objectives: The research aims to analyze the catabolic strength of different hydrolytic enzymes in assessing the biological conversion potential of lignocellulose parts of agricultural biomass wastes into functional edible sugars and biofuels. Materials and Methods: The enzymes' hydrolytic properties—versatile peroxidase, manganese peroxidase, and lignin peroxidase were used to identify their complexing strength with the lignin substrate, whereas endoglucanase cel12A, acidocaldarius cellulase, and Melanocarpus albomyces endoglucanase were tested on the cellulose gel substrate. Because the biodegradation properties are heavily influenced by the "enzyme-substrate complexing energy level," proper molecular optimization and energy minimization of the enzymes and substrates were carried out, as well as the identification of the enzyme's active sites prior to complexing. comprehensive molecular dynamic simulation was run to study their—alpha carbon, root-mean-square deviation (Å), molecular surface area (Å2), root-mean-square fluctuation (Å), radius of gyration (nm), hydrogen bonds with hydrophobic interactions, and solvent accessible surface area (Å2) values for 50 ns. The simulated data mining was conducted using advanced programming algorithms to establish the final enzyme-substrate complexing strength in binding and catalysis. Results: Among the lignin-degrading enzymes, versatile peroxidase shows promising catalytic activity with the best docking pose and significant values in all the dynamic simulation parameters. Similarly, Melanocarpus albomyces endoglucanase shows the best activity in all aspects of molecular docking and dynamics among the cellulose-degrading enzymes. Conclusion: The lignin content of biomass wastes can be degraded into cellulose and hemicellulose using lignin-degrading enzymes. The cellulose can be further degraded into glucose and xylose sugars following the cellulose-degrading enzyme activity. These sugars can be further degraded into biofuel through anaerobic fermentation. Systematic bioconversion of the lignocellulosic components can ensure sustainable biomass management, creating an alternative food and energy source for human beings to face the challenges of global hunger where the enzymes can pave the way. [J Adv Vet Anim Res 2022; 9(1.000): 19-32]

Mitochondria are major contributors to ATP synthesis, generating more than 90% of the total cellular energy production through oxidative phosphorylation (OXPHOS): metabolite oxidation, such as the β-oxidation of fatty acids, and the Krebs’s cycle. OXPHOS inadequacy due to large genetic lesions in mitochondrial as well as nuclear genes and homo- or heteroplasmic point mutations in mitochondrially encoded genes is a characteristic of heterogeneous, maternally inherited genetic disorders known as mitochondrial disorders that affect multisystemic tissues and organs with high energy requirements, resulting in various signs and symptoms. Several traditional diagnostic approaches, including magnetic resonance imaging of the brain, cardiac testing, biochemical screening, variable heteroplasmy genetic testing, identifying clinical features, and skeletal muscle biopsies, are associated with increased risks, high costs, a high degree of false-positive or false-negative results, or a lack of precision, which limits their diagnostic abilities for mitochondrial disorders. Variable heteroplasmy levels, mtDNA depletion, and the identification of pathogenic variants can be detected through genetic sequencing, including the gold standard Sanger sequencing. However, sequencing can be time consuming, and Sanger sequencing can result in the missed recognition of larger structural variations such as CNVs or copy-number variations. Although each sequencing method has its own limitations, genetic sequencing can be an alternative to traditional diagnostic methods. The ever-growing roster of possible mutations has led to the development of next-generation sequencing (NGS). The enhancement of NGS methods can offer a precise diagnosis of the mitochondrial disorder within a short period at a reasonable expense for both research and clinical applications.

Taeniophyllum is one of the smallest orchids in the world. This genus has around 210 species listed in the plant list. One type of this orchid is found in the Juanda Forest Park (THRJ) Bandung. This orchid is difficult to identify at the species level due to its limited morphological character and very small size. Taxonomy and conservation status of this plant are unknown so that it can be used as a model for developing DNA barcodes for this genus. In this study, two DNA barcodes (matK and ITS) were used to reconstruct the phylogenetic relationship of Taeniophyllum THRJ. By using matK sequences, Taeniophyllum THRJ was grouped together with Taeniophyllum glandulosum and T. aphyllum. However, using the ITS sequence, Taeniophyllum THRJ was positioned together with Microtatorchis sp., T. smithii, and T. complanatum. The results showed that the matK gene can be used for DNA barcoding of Taeniophyllum orchids. The use of ITS sequence for Taeniophyllum group still cannot be confirmed yet. Based on matK sequences and possibly ITS sequences, it can be concluded that Taeniophyllum THRJ is not T. glandulosum, but is another species of Taeniophyllum. [ J Adv Biotechnol Exp Ther 2021; 4(2.000): 171-177]

Abstract Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

Abstract Introduction Many of the global pandemics threaten human existence over the decades among which coronavirus disease (COVID‐19) is the newest exposure circulating worldwide. The RNA encoded severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus is referred as the pivotal agent of this deadly disease that induces respiratory tract infection by interacting host ACE2 receptor with its spike glycoprotein. Rapidly evolving nature of this virus modified into new variants helps in perpetrating immune escape and protection against host defense mechanism. Consequently, a new isolate, delta variant originated from India is spreading perilously at a higher infection rate. Methods In this study, we focused to understand the conformational and functional significance of the missense mutations found in the spike glycoprotein of SARS‐CoV‐2 delta variant performing different computational analysis. Results From physiochemical analysis, we found that the acidic isoelectric point of the virus elevated to basic pH level due to the mutations. The targeted mutations were also found to change the interactive bonding pattern and conformational stability analyzed by the molecular dynamic's simulation. The molecular docking study also revealed that L452R and T478K mutations found in the RBD domain of delta variant spike protein contributed to alter interaction with the host ACE2 receptor. Conclusions Overall, this study provided insightful evidence to understand the morphological and attributive impact of the mutations on SARS‐CoV‐2 delta variant.

The environment-friendly bacterial strains are used for wastewater treatment due to their high degrading capability and cost-effectiveness. In the present study, we isolated, identified, characterized, and optimized culture condition ( Temperature 35 °C for both, time up to 96 h, pH 7 and 7.5 respectively) of two dye degrading bacteria from industrial effluents. Morphological, biochemical, and molecular identification confirmed those strains as Bacillus pseudomycoides and Acinetobacter haemolyticus. Spectrophotometric methods were used to investigate the dye degradation(single and mixed dye) capability of these two bacteria. These strains were the potential for degrading methylene green (MG), basic violet (BV) and acid blue (AB) dyes. In case of MG + BV, B. pseudomycoides, and A. haemolyticus showed a degradation rate of 74% and 75%, respectively. While degradation was found 75% and 82% for MG + AB combination, 73% and 73% for AB + BV combination, and 80% and 82% for MG + BV + AB combination respectively. Azoreductase enzymes from bacteria are essential for breaking down the azo bond in textile azo dyes. In molecular docking, the binding energy of three docking complexes (protein and MG, protein and BV, protein and AB) were −6.3, −6.6, and −6.8 Kcal/mol, respectively. The binding stability of the docked complexes was ensured by the root mean square deviations (RMSD), solvent accessible surface area (SASA), radius of gyration (Rg) and hydrogen bond in a molecular dynamics simulation study, indicating strong and stable binding. This study revealed that both B. pseudomycoides and A. haemolyticus could decolorize single and mixed dyes efficiently. As a result, both the strains could be used in further research to apply their potentiality in large-scale dye degradation in the future.

The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of Phyllanthus amarus and its phytoconstituents through an in vitro and in silico approach. The in vitro acetylcholinesterase inhibitory activity of P amarus was carried out, followed by the molecular docking studies of its phytoconstituents. The top-ranked molecules identified through molecular docking were subjected to molecular dynamics simulation (MDS) and density functional theory (DFT) studies. The results obtained revealed the methanolic extract of P amarus as a potent acetylcholinesterase inhibitor, while amarosterol A, hinokinin, β-sitosterol, stigmasterol and ellagic acid were identified as potential acetylcholinesterase inhibitors. The MDS and DFT results are in agreement with those obtained from the docking studies. Our findings suggest further studies on the hit molecules.

Fibroblast growth factor receptors (FGFR) are an essential player in oncogenesis and tumor progression. LY2874455 was identified as a pan-FGFR inhibitor and has gone through phase I clinical trial. In the current study, virtual screening was conducted against the PubChem database using a pharmacophore model generated from the crystal structure of FGFR4 inhibited by LY2874455. PubChem 137300327 was identified as the most suitable compound from this screening. Later, molecular docking and molecular dynamics studies conducted with FGFRs corroborated the initial finding. Analysis of ADMET properties disclosed that LY2874455 and PubChem 137300327 share alike properties. Our study suggests that PubChem 137300327 is a potential pan-FGFR inhibitor and can be exploited to treat different cancers following validation in proper wet-lab experiments and study in animal cancer models. This compound also follows Lipinski’s rules and can be used as a lead compound to synthesize more effective anticancer compounds.

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.

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.

The numerous bioactive components from Bacillus subtilis are commonly used as antimicrobial agents for reducing plant diseases caused by fungal pathovars. In this study, we isolated and identified B. subtilis SI-18 strain from twenty isolates of rhizosphere soil through morphological and molecular approaches, and explored its inhibitory activities against Rhizoctonia solani. According to morphological features and 16S rRNA and gyrB gene sequence analysis, B. subtilis SI-18 strain was identified. Additionally, the culture filtrate of B. subtilis SI-18 resulted in the suppression of R. solani mycelium growth and material leakage from the cells. Then, we have performed homology modelling and molecular docking study of S9 protein from R. solani where three potential compounds (D1, D2, and D3) were identified among 134 antimicrobial compounds derived from B. subtilis group based on higher binding energy and interaction at the active grove of the target protein. The D1 compound creates alkyl bond at Val48 whereas D2 also binds with Val48 by creating hydrogen bond. On the other hand, two hydrogen bonds were observed at Val48 and Ile52 by D3, which might be responsible for possible blocking of the target S9 protein of R. solani. To validate the docking study and understand the change in drug-ligand conformation, molecular dynamics simulation was assessed where rigid conformation was found for D1, D2 and D3 complexes. Moreover, ADMET study confirms that no toxicity and carcinogenicity were found for screened compounds. Based on our studies, we demonstrated that compounds D1, D2, and D3 derived from B. subtilis can be a potential inhibitor of S9 protein of R. solani that might be a possible strategy for fungal disease prevention.

This investigation was carried out to observe the migration status and the feeding guild of the avian fauna including the relative diversity of Jaipurhat District of Bangladesh. Data were collected from November 2017 to October 2019. During the study period, 89 avian species were recorded that belong to 32 families under 11 orders among which 8 (8.99%) species were common winter visitors, 3 (3.37%) were common summer visitors, 8 (8.99%) were resident migratory, 1 (1.12%) were rare resident and 69 (77.53%) were resident birds. Among the birds observed in the study area during the study period the highest number of birds was found to be insectivorous (41.57%), then the carnivorous (8.99%), then omnivorous, piscivorous and picio carnivorous (7.87%), then insecto frugivorous (6.67%), then frugivorous (5.62%), then frugio graminivorous (4.49%), then nectarivorous (3.39%), then graminivorous and molluscio carnivorous (2.25%) and insecto carnivorous (1.12%). The hight avian diversity (69.662%) was observed in Mithapur which is human inhabited area with crop lands and a lot of fruit trees and the lowest (32.584%) diversity was in Shree Rampur Bill and Kastogari Bill which has large water bodies. [ J Adv Biotechnol Exp Ther 2020; 3(3.000): 204-215]

Since ancient times, soil bacteria play an important role on crop growth and yield by genetic transformation naturally. But the continuous use of chemical fertilizers reduces their number and proper environment for multiplication. Seed treatment with beneficial bacteria provides nutrients for the growth of crop plants. So soil bacteria were isolated, their growth characteristics and effect on wheat growth were observed. The maximum growth of Isolate A and Isolate B was observed at pH 5.5, 7.0 and 33°C, 35°C respectively. Morphological characteristics indicated that Isolate A and Isolate B were gram-positive. But both bacteria were non-motile. In Biochemical test, both of them showed positive result in the methyl red test, catalase test, urea test, starch hydrolysis test, and negative in TSI (Triple Sugar Iron) test, mannitol salt test. Isolate B showed positive result in BSA, MacConkey test and EMB (Eosin Methylene Blue) test and Isolate A showed negative result in BSA (Bismuth Sulphite Agar), MacConkey test and EMB test. Besides, both of the bacteria were multi-drug resistance showing resistance to penicillin, amoxicillin, ampicillin cefuroxime, and ceftazidime.16S rRNA gene sequencing identified the isolate A and Isolate B as Bacillus thuringiensis and Bacillus anthracis. After 6 hours of wheat seed treatment germination percentage, fresh root and shoot weight, root and shoot dry weight, relative water content of both root and shoot, and plant growth was enhanced by Bacillus thuringiensis and Bacillus anthracis. Bacillus anthracis was more capable than bacillus thuringiensis for increasing germination rates, both root and shoot growth of wheat. It indicated that Bacillus anthracis and Bacillus thuringiensis mediated growth improvement of wheat is possibly originated in roots. [ J Adv Biotechnol Exp Ther 2020; 3(3.000): 254-262]

The overexpression of matrix metalloproteinase-9 (MMP-9) is associated with tumor development and angiogenesis, and hence, it has been considered an attractive drug target for anticancer therapy. To assist in drug design endeavors for MMP-9 targets, an in silico study was presented to investigate whether our compounds inhibit MMP-9 by binding to the catalytic domain, similar to their inhibitor or not. For that, in the initial stage, a deep-learning algorithm was used for the predictive modeling of the CHEMBL321 dataset of MMP-9 inhibitors. Several regression models were built and evaluated based on R2, MAE MSE, RMSE, and Loss. The best model was utilized to screen the drug bank database containing 9,102 compounds to seek novel compounds as MMP-9 inhibitors. Then top high score compounds were selected for molecular docking based on the comparison between the score of the reference molecule. Furthermore, molecules having the highest docking scores were selected, and interaction mechanisms with respect to S1 pocket and catalytic zinc ion of these compounds were also discussed. Those compounds, involving binding to the catalytic zinc ion and the S1 pocket of MMP-9, were considered preferentially for molecular dynamics studies (100 ns) and an MM-PBSA (last 30 ns) analysis. Based on the results, we proposed several novel compounds as potential candidates for MMP-9 inhibition and investigated their binding properties with MMP-9. The findings suggested that these compounds may be useful in the design and development of MMP-9 inhibitors in the future.

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.

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/β-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 β-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 β-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.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic due to the high transmission and mortality rate of this virus. The world health and economic sectors have been severely affected by this deadly virus, exacerbated by the lack of sufficient efficient vaccines. The design of effective drug candidates and their rapid development is necessary to combat this virus. In this study, we selected 23 antimicrobial peptides from the literature and predicted their structure using PEP-FOLD 3.5. In addition, we docked them to the SARS-CoV-2 spike protein receptor-binding domain (RBD) to study their capability to inhibit the RBD, which plays a significant role in virus binding, fusion and entry into the host cell. We used several docking programs including HDOCK, HPEPDOCK, ClusPro, and HawkDock to calculate the binding energy of the protein-peptide complexes. We identified four peptides with high binding free energy and docking scores. The docking results were further verified by molecular dynamics (MD) simulations to characterize the protein-peptide complexes in terms of their root-mean-square fluctuation (RMSF), root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond formation. Allergenicity and toxicity predictions suggested that the peptides we identified were non-allergenic and non-toxic. This study suggests that these four antimicrobial peptides could inhibit the RBD of SARS-CoV-2. Future in vitro and in vivo studies are necessary to confirm this.

Bagasse is a byproduct generated during the process of making the traditional Andean drink named “chicha de jora” in Peru, which is a potential source for the extraction of ferulated arabinoxylan (FAX). The aim of this study was to extract and characterize the FAX from bagasse and determine its antioxidant and antihyperglycemic capacity in vitro. As a result, FAX of molecular weight ≥3.5 kDa presented moisture content, pH, total ash, proteins, and total phenolic content with values of 8.00%, 5.81, 2.68%, 3.78%, and 5.72 mg EAG/g, respectively. Thin-layer chromatography identified the monosaccharides L-arabinose and D-xylose. HPLC-MS/MS analysis of FAX confirmed the presence of methyl-pentofuranosides or methyl-pentopyranosides. The FT-IR spectrum presented characteristic bands of FAX. The FAX showed antioxidant capacity determined by the DPPH assay (IC50 = 6.59 mg/mL and TEAC = 7.7844 μmol/g sample), ABTS (IC50 = 6.50 mg/mL and TEAC 35.34 μmol/g sample), and FRAP (14.08 μmol AA/g and 36.63 μmol FeSO4/g). On the other hand, FAX showed glucose adsorption capacity, inhibition of glucose diffusion, and inhibition of the enzyme α-amylase (IC50 = 4.73 mg/mL). The results showed that the FAX extracted from the bagasse generated during the production of the “chicha de jora” has in vitro antioxidant and antihyperglycemic capacity.

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 investigation of traditional medicinal plants is gaining prime importance day by day due to having a wide range of bioactive phytochemicals. The presence of diverse bioactive compounds makes medicinal plants more demandable for curing several diseases, such as inflammatory diseases, diabetes, and cancer. Leucas indica is commonly found throughout Bangladesh and traditionally used for medical purposes because of its great medicinal value to the folks. The present study addresses the evaluation of in vitro qualitative phytochemical, antioxidant, and cytotoxicity activities as well as in silico anticancer activity of methanolic leaf extract. Several standard methods were used for phytochemical analysis, which showed the presence of different phytochemicals. The plant exhibited adequate antioxidant activities through DPPH and H2O2 free radical scavenging assays. Moreover, promising cytotoxicity activity was estimated through a brine shrimp lethality assay. In addition, the present work emphasizes the in silico analysis, which finds the anticancer activity of the experimental plant based on pharmacokinetic analysis, molecular docking, and MD simulation. Four phytochemicals of the plant were selected from the literature and docked against two important protein kinases (AMPK and CDK6) that have a role in cancer progression. The docking revealed an encouraging binding score with a maximum score of 9.2 kCal/mol, where all the ligand-protein complexes showed stable conditions during simulation. According to this analysis, it can be believed that the selected ligands indicate promising anticancer activity. Moreover, the comprehensive analysis of both in vitro and in silico data shows that the leaf could be a potent source of drug and could serve as an effective therapeutic in the future.

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.

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. Mpro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making Mpro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of −8.3, −8.6, and −8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.

The species of Trichoderma are one of the most frequently used natural biocontrol agent. This study, we identified isolate HbGT6-07 of Trichoderma asperellum and evaluated the antimicrobial effects both in vitro and in silico approaches. Tested 10% concentrated culture filtrate of HbGT6-07 inhibited 98% of colony radial growth in B. cinerea (B05.10) as well as 91% of S. sclerotiorum (A367). HbGT6-07 was detected to produce volatile organic compounds (VOCs) with antifungal activity. In in-vitro dish-within-dish method (DwD), The HbGT6-07 VOCs effectively reduced colonial diameter, growth rate and sclerotia production by two virulent fungal pathogens. Moreover, the hyphal fragments of HbGT6-07 demonstrated successful mycelia growth suppression (97%) against infection oilseed rape leaves by hyphae of the two virulent fungal pathogens through competition. The mixed culture assay, exhibited that the isolate T. asperellum HbGT6-07 was significantly reduced the production and weight of sclerotia. The GC-MS analysis identified 32 VOCs derived from HbGT6-07. In addition, VOCs derived from HbGT6-07 were assessed against targeted protein of three fungal species; Aspergillus oryzae, Saccharomyces cerevisiae, Candida albicans via molecular docking. Butylated hydroxytolune and Beta-Cedrene had energy (−5.3 and −5.7 Kcal/mol) for targeted protein of Aspergillus oryzae and (−6.8 and −8.0 Kcal/mol) for Saccharomyces cerevisiae, whereas alpha-bergamotene and Beta-Cedrene exihbit energy (−7.5 and −7.4 Kcal/mol), respectively. The molecular dynamics study confirms the structural stability and rigidity of the docked complex through multiple descriptors from simulation trajectories. The above findings indicated that HbGT6-07 could attain competitive progress via production of VOCs and comprehensive mycelial growth.

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.

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

The search for natural plant-based products as new pharmacological alternatives to treat various human pathologies has taken on great importance for researchers and research laboratories. In this context, research has intensified to extract and identify natural molecules endowed with biological effects. The objective of this study is to review the source and pharmacological properties of cirsimaritin. The identification and isolation of this flavonoid from various natural sources, including medicinal plants such as Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and Ocimum sanctum, has been carried out and verified using different spectral techniques. Biological effect investigations are carried out with a wide variety of experimental models in vitro and in vivo and laboratory techniques. The results of these research works showed the biological properties of cirsimaritin including anticancer, antimicrobial, antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms involved in the multiple activities of this molecule are diverse and include sub-cellular, cellular, and molecular levels. Indeed, this bioactive induces anti-inflammatory and antiproliferative effects by inhibiting cell membrane receptors, interference with signaling pathways, and inhibiting transcriptional factors such as Nf-κB involved in cell promotion and proliferation. In the light of these results, cirsimaritin appears as a promising and viable alternative natural bioactive drug to treat many pathological conditions.

Eucalyptus globulus is a plant widely used by the world population, including Morocco, in the treatment of several pathologies. The aim of this work is to evaluate the antioxidant, anti-inflammatory, dermatoprotective, and antimicrobial effects of essential oil and honey from E. globulus, as well as their combination. Chemical composition was determined by GC-MS analysis. The antioxidant activity was evaluated by three tests, namely, DPPH, reducing power, and the β-carotene/linoleic acid assay. The anti-inflammatory activity was investigated in vitro (5-lipoxygenase inhibition) and in vivo (carrageenan-induced paw edema model), while the dermatoprotective activity was tested in vitro (tyrosinase inhibition). Moreover, the antibacterial activity was assessed using agar well diffusion and microdilution methods. The results showed that eucalyptol presents the main compound of the essential oil of E. globulus (90.14%). The mixture of essential oil with honey showed the best antioxidant effects for all the tests used (0.07 < IC50 < 0.19 mg/mL), while the essential oil was the most active against tyrosinase (IC50 = 38.21 ± 0.13 μg/mL) and 5-lipoxygenase (IC50 = 0.88 ± 0.01 μg/mL), which corroborated the in vivo test. Additionally, the essential oil showed the best bactericidal effects against all strains tested, with inhibition diameter values ranging from 12.8 to 21.6 mm. The findings of this work showed that the combination of the essential oil with honey showed important results in terms of biological activity, but the determination of the underlying mechanisms of action remains a major prospect to be determined.

Piper betle L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for type 2 diabetes patients. In this study, compounds of P. betle were screened to investigate the inhibitory action of alpha-amylase and alpha-glucosidase against type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7-O-glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target proteins alpha-amylase and alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = −45.02 kcal mol−1 for alpha-amylase and −38.288 for alpha-glucosidase) compared with control inhibitor acarbose, which had binding affinities of −36.796 kcal mol−1 for alpha-amylase and −29.622 kcal mol−1 for alpha-glucosidase. The apigenin-7-O-glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors’ native ligand. Based on ADMET analysis, this phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities and had no significant side effects, making them prospective drug candidates for type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.

The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex’s stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2.

Streptococcus pneumoniae (Pneumococcus) accounts for a major global health burden that causes bacterial pneumonia, sepsis, otitis media, and meningitis. It is responsible for great morbidity and mortality globally. Available pneumonia vaccines are either carbohydrate-based vaccines or not protective against specific serotypes. Besides, antibiotic resistance to pneumococci justifies further attention to explore new vaccine candidates. The invariant peptide-based vaccines are not only immunogenic for all age groups but also protective against all serotypes of pneumococci. Initially, we searched for potential vaccine candidates of pneumococcus through literature mining. We found Choline binding protein A (CbpA) as a potential immunogenic extracellular protein. Next we applied the immunoinformatic approach to design a multi-epitope based vaccine (MEV) candidate of CbpA against pneumococcus. Furthermore, the protein sequence revealed the immunogenic T-cell epitopes of CbpA. The affinity between the T-cell epitope and MHC molecule was evaluated by Molecular docking (MD) analyses. We found a single 15-mer T-cell epitope (AMATGWLQYNGSWYY), which has not only affinity for both MHC class I and class II but also has the highest population coverage. Besides, the B-cell and IFNγ-inducing epitopes were also selected. All the peptides were assessed for conservancy, allergenicity, immunogenicity, and hydrophobicity. Finally, we assembled the best T-cell, B-cell, and IFNγ-inducing epitopes to make an MEV. The docking and MD simulation study revealed a strong affinity between the MEV and Toll-like receptors. Therefore, we propose that MEV of CbpA could be a novel vaccine candidate, which may induce both humoral and cellular immune responses to non-serotype-specific pneumococcus.

Zika virus (ZIKV) is an arboviral pathogen that belongs to the Flaviviridae subgroup and is a contemporary global concern. Recent epidemic outbreaks in Brazil have indicated that ZIKV could be responsible for post-infection neurological disorders in infants, resulting in ZIKV being considered a major threat to global health. Unfortunately, no vaccine is yet available to prevent the spread of this virus. In this study, we have applied an in silico approach to the identification of B-cell epitopes in the ZIKV genome. By utilizing currently available genomic data and applying multiple sequence alignments and the Immune Epitope Database (IDEB) tools, a LEFYSYKKSG epitope was identified in a highly conserved peptide region of the ZIKV polyprotein. The antigenicity, allergenicity, and affinity of the B-cell epitope were evaluated, and significant B-cell affinity against ZIKV was identified. This highly conserved epitope can be used to develop a peptide-based vaccine and can also be applied toward the development of a monoclonal antibody (mAb) for therapeutic or diagnostic purposes against ZIKV.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for the analgesic, antipyretic and anti-inflammation treatment. It is effectively used in acute and chronic pain. It inhibits the prostaglandin synthesis by blocking cyclooxygenase (COX). However, it shows some crucial side effects like renal, gastrointestinal and cardiovascular injury to the human and other living things. It also causes gastrointestinal side effects like bleeding and perforation if taken at higher dose for a long period of time. Liver toxicity is also another issue related to oral diclofenac. To improve its safety profile, an attempt has been taken to design some new potential drug to reduce the side effects with better medicinal action. The insertion of new functional groups such as CH3, OCH3, F, CF3, OCF3, Cl, OH, COOH, NH2, CH2NH2, CONH2, NHCOCH3 at the different positions of its core structure significantly enhance the chemical and biological performance. Chemical, physical and spectral calculation has been performed by geometry optimization to characterize the newly designed structures. Molecular docking and dynamics simulation have been performed against human prostaglandin synthase protein (PDB ID: 5F19) to predict binding affinity, bonding interaction and stability of protein-drug complex. ADMET predictions have been studied to search for their pharmacokinetic properties like absorption, metabolism and toxicity. Physicochemical and spectral data support the new structural conformation. Molecular docking and dynamics studies disclose improved medicinal effect and pharmacokinetic prediction suggest their reduced side effects and non-carcinogenic properties than the parent drug which lead to develop the novel drug with improved clinical safety.

Bisphenols are widely used in polymer and packaging industries. But they are contaminating the environment and food chain by degradation, particularly affecting to the human endocrine system. Herein, we have investigated the physicochemical, spectral, biological and pharmacokinetic properties of some selected bisphenol analogues utilizing computer-aided drug design methods. Geometry optimization has been performed by employing density functional theory with B3LYP/6-311g++ (d, p) basis set. Geometrical, thermodynamical, molecular orbital and electrostatic potential studies have been calculated to investigate their physical and chemical behavior. Meanwhile, FT-IR, Raman and UV-Vis's spectra have been measured and compared with the experimental values. Molecular docking and dynamics simulation studies have been performed against human estrogen-related receptor protein to investigate their binding affinity, mode and interactions with the receptor. ADMET prediction has been performed to compare their absorption, distribution, metabolism and toxicity. Among the studied analogues, Bis AF has the highest free energy and Bis E has highest binding affinity. Meanwhile, Bis S shows the highest dipole moment and the chemical reactivity. Most of them have inhibitory property to the CYP2C9 and Bis S shows the carcinogenic property. Based on the comparative physicochemical, spectral, biological and ADMET calculation, this study can be helpful to understand more deeply about their biochemical impact on the environment and human being.

In this in silico study, thirty-five ciprofloxacin analogs were docked to the active site of DNA gyrase, the prime target of ciprofloxacin type antibiotics. Prior to docking all the structures were optimized using MM2 force field parameters. The study revealed that five candidates, namely 6MePQ_3, 6MePQ_11, A6MePQ_3, HPQ_11, and PQ_7, exhibited promising binding to DNA gyrase. Upon analysis of the ligand-receptor complex, it is also divulged that this binding has been stabilized by the interaction between different neutral, nonpolar, aromatic amino-acid residues of DNA gyrase and the ciprofloxacin analogs. Moreover, the interaction between ciprofloxacin analogs and DNA gyrase was mainly governed by hydrophobic interactions and, to a lesser extent, hydrogen bonds. Halogen bonds, electrostatic interactions, and other types of interactions were almost absent in all cases. Molecular dynamic simulation was performed to recognize the structural variations and the complexes' stability of suggested ligands. This study indicates that 6MePQ_3 forms a stable drug-protein complex. On the other site, Pharmacokinetic filtering done using SwissADME server, reveals that 6MePQ_3 is well absorbed from the GI tract, does not cross BBB and is not a P-gp substrate. But it is possible to check and confirm its all “in silico” pharmacodynamics and pharmacokinetics characteristics in real life by synthesis and subsequent analysis of this ligand.

One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7–12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.

Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski’s rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (−)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with no signs of abatement in sight. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of this pandemic and has claimed over 5 million lives, is still mutating, resulting in numerous variants. One of the newest variants is Omicron, which shows an increase in its transmissibility, but also reportedly reduces hospitalization rates and shows milder symptoms, such as in those who have been vaccinated. As a result, many believe that Omicron provides a natural vaccination, which is the first step toward ending the COVID-19 pandemic. Based on published research and scientific evidence, we review and discuss how the end of this pandemic is predicted to occur as a result of Omicron variants being surpassed in the community. In light of the findings of our research, we believe that it is most likely true that the Omicron variant is a natural way of vaccinating the masses and slowing the spread of this deadly pandemic. While the mutation that causes the Omicron variant is encouraging, subsequent mutations do not guarantee that the disease it causes will be less severe. As the virus continues to evolve, humans must constantly adapt by increasing their immunity through vaccination.

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.

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation.

A series of methyl β-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which was subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in Wuhan, China, in December 2019. Elderly individuals and those with comorbid conditions may be more vulnerable to this disease. Consequently, several research laboratories continue to focus on developing drugs to treat this infection because this disease has developed into a global pandemic with an extremely limited number of specific treatments available. Natural herbal remedies have long been used to treat illnesses in a variety of cultures. Modern medicine has achieved success due to the effectiveness of traditional medicines, which are derived from medicinal plants. The objective of this study was to determine whether components of natural origin from Iranian medicinal plants have an antiviral effect that can prevent humans from this coronavirus infection using the most reliable molecular docking method; in our case, we focused on the main protease (Mpro) and a receptor-binding domain (RBD). The results of molecular docking showed that among 169 molecules of natural origin from common Iranian medicinal plants, 20 molecules (chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, etc.) can be proposed as inhibitors against this coronavirus based on the binding free energy and type of interactions between these molecules and the studied proteins. Moreover, a molecular dynamics simulation study revealed that the chelidimerine–Mpro and somniferine–RBD complexes were stable for up to 50 ns below 0.5 nm. Our results provide valuable insights into this mechanism, which sheds light on future structure-based designs of high-potency inhibitors for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus’s severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography–mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics–generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (−5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (−5.39 kcal/mol), and lorazepam, 2TMS derivative (−5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand–Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.

Currently, a worldwide pandemic has been declared in response to the spread of coronavirus disease 2019 (COVID-19), a fatal and fast-spreading viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The low availability of efficient vaccines and treatment options has resulted in a high mortality rate, bringing the world economy to its knees. Thus, mechanistic investigations of drugs capable of counteracting this disease are in high demand. The main protease (Mpro) expressed by SARS-CoV-2 has been targeted for the development of potential drug candidates due to the crucial role played by Mpro in viral replication and transcription. We generated a phytochemical library containing 1672 phytochemicals derived from 56 plants, which have been reported as having antiviral, antibacterial, and antifungal activity. A molecular docking program was used to screen the top three candidate compounds: epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate, which had respective binding affinities of −8.4, −8.5, and −8.8 kcal/mol. Several active sites in the targeted protein, including Cys145, His41, Met49, Glu66, and Met165, were found to interact with the top three candidate compounds. The multiple simulation profile, root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and solvent-accessible surface area values supported the inflexible nature of the docked protein–compound complexes. The toxicity and carcinogenicity profiles were assessed, which showed that epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate had favorable pharmacological properties with no adverse effects. These findings suggest that these compounds could be developed as part of an effective drug development pathway to treat COVID-19.

The recent coronavirus disease 2019 (COVID-19) pandemic is a global threat for healthcare management and the economic system, and effective treatments against the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for this disease have not yet progressed beyond the developmental phases. As drug refinement and vaccine progression require enormously broad investments of time, alternative strategies are urgently needed. In this study, we examined phytochemicals extracted from Avicennia officinalis and evaluated their potential effects against the main protease of SARS-CoV-2. The antioxidant activities of A. officinalis leaf and fruit extracts at 150 µg/mL were 95.97% and 92.48%, respectively. Furthermore, both extracts displayed low cytotoxicity levels against Artemia salina. The gas chromatography–mass spectroscopy analysis confirmed the identifies of 75 phytochemicals from both extracts, and four potent compounds, triacontane, hexacosane, methyl linoleate, and methyl palminoleate, had binding free energy values of −6.75, −6.7, −6.3, and −6.3 Kcal/mol, respectively, in complexes with the SARS-CoV-2 main protease. The active residues Cys145, Met165, Glu166, Gln189, and Arg188 in the main protease formed non-bonded interactions with the screened compounds. The root-mean-square difference (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond data from a molecular dynamics simulation study confirmed the docked complexes′ binding rigidity in the atomistic simulated environment. However, this study′s findings require in vitro and in vivo validation to ensure the possible inhibitory effects and pharmacological efficacy of the identified compounds.

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.