Multi-targeted therapeutic potential of stigmasterol from the Euphorbia ammak plant in treating lung and breast cancer.

Cancer is the most prevalent disease globally, which presents a significant challenge to the healthcare industry, with breast and lung cancer being predominant malignancies. This study used RNA-seq data from the TCGA database to identify potential biomarkers for lung and breast cancer. Tumor Necrosis Factor (TNFAIP8) and Sulfite Oxidase (SUOX) showed significant expression variation and were selected for further study using structure-based drug discovery (SBDD). Compounds derived from the Euphorbia ammak plant were selected for in-silico study with both TNFAIP8 and SUOX. Stigmasterol had the greatest binding scores (normalized scores of -8.53 kcal/mol and -9.69 kcal/mol) with both proteins, indicating strong stability in their binding pockets throughout the molecular dynamics' simulation. Although Stigmasterol first changed its initial conformation (RMSD = 0.5 nm with the starting conformation) in SUOX, it eventually reached a stable conformation (RMSD of 1.5 nm). The compound on TNFAIP8 showed a persistent shape (RMSD of 0.35 nm), indicating strong protein stability. The binding free energy of the complex was calculated using the MM/GBSA technique; TNFAIP8 had a ΔGTOTAL of -24.98 kcal/mol, with TYR160 being the most significant residue, contributing -2.52 kcal/mol. On the other hand, the SUOX complex had a binding free energy of -16.87 kcal/mol, with LEU151 being the primary contributor (-1.17 kcal/mol). Analysis of the complexes' free energy landscape unveiled several states with minimum free energy, indicating robust interactions between the protein and ligand. In its conclusion, this work emphasises the favourable ability of Stigmasterol to bind with prospective targets for lung and breast cancer, indicating the need for more experimental study.

Prediction of anticancer peptides derived from the true lectins of Phoenix dactylifera and their synergetic effect with mitotane.

Background and aims: Cancer continues to be a significant source of both illness and death on a global scale, traditional medicinal plants continue to serve as a fundamental resource of natural bioactive compounds as an alternative source of remedies. Although there have been numerous studies on the therapeutic role of Phoenix dactylifera, the study of the role of peptides has not been thoroughly investigated. This study aimed to investigate the anticancer activity of lectin peptides from P. dactylifera using in silico and in vivo analysis. Methods: Different computational tools were used to extract and predict anticancer peptides from the true lectins of P. dactylifera. Nine peptides that are bioactive substances have been investigated for their anticancer activity against MCF-7 and T47D (two forms of breast cancer). To counteract the unfavorable effects of mitotane, the most potent peptides (U3 and U7) were combined with it and assessed for anticancer activity against MCF-7 and HepG2. Results: In silico analysis revealed that nine peptides were predicted with anticancer activity. In cell lines, the lowest IC50 values were measured in U3 and U7 against MCF-7 and T47D cells. U3 or U7 in combination with mitotane demonstrated the lowest IC50 against MCF-7 and HepG2. The maximum level of cell proliferation inhibition was 22% when U3 (500 µg/mL) and 25 µg/mL mitotane were combined, compared to 41% when 25 µg/mL mitotane was used alone. When mitotane and U3 or U7 were combined, it was shown that these bioactive substances worked synergistically with mitotane to lessen its negative effects. The combination of peptides and mitotane could be regarded as an efficient chemotherapeutic medication having these bioactive properties for treating a variety of tumors while enhancing the reduction of side effects.

Fragment-based drug design of novel inhibitors targeting lipoprotein (a) kringle domain KIV-10-mediated cardiovascular disease.

Cardiovascular diseases (CVDs) are the leading cause of death globally, attributed to a complex etiology involving metabolic, genetic, and protein-related factors. Lipoprotein(a) (Lp(a)), identified as a genetic risk factor, exhibits elevated levels linked to an increased risk of cardiovascular diseases. The lipoprotein(a) kringle domains have recently been identified as a potential target for the treatment of CVDs, in this study we utilized a fragment-based drug design approach to design a novel, potent, and safe inhibitor for lipoprotein(a) kringle domain. With the use of fragment library (61,600 fragments) screening, combined with analyses such as MM/GBSA, molecular dynamics simulation (MD), and principal component analysis, we successfully identified molecules effective against the kringle domains of Lipoprotein(a). The hybridization process (Breed) of the best fragments generated a novel 249 hybrid molecules, among them 77 exhibiting superior binding affinity (≤ -7 kcal/mol) compared to control AZ-02 (-6.9 kcal/mol), Importantly, the top ten molecules displayed high similarity to the control AZ-02. Among the top ten molecules, BR1 exhibited the best docking energy (-11.85 kcal/mol ), and higher stability within the protein LBS site, demonstrating the capability to counteract the pathophysiological effects of lipoprotein(a) [Lp(a)]. Additionally, principal component analysis (PCA) highlighted a similar trend of motion during the binding of BR1 and the control compound (AZ-02), limiting protein mobility and reducing conformational space. Moreover, ADMET analysis indicated favorable drug-like properties, with BR1 showing minimal violations of Lipinski's rules. Overall, the identified compounds hold promise as potential therapeutics, addressing a critical need in cardiovascular medicine. Further preclinical and clinical evaluations are needed to validate their efficacy and safety, potentially ushering in a new era of targeted therapies for CVDs.

Association of Normal and Mutated APOL1 G2 Rs60910145 alleles with SCD, Body Mass Index, and Renal Function Biomarkers and Indices.

PURPOSE OF THE STUDY: The current study aimed to detect the frequency of normal and mutated APOL1 alleles in sickle cell disease (SCD) patients and test their relation with Microalbuminuria, Creatinine, Urea, Glomerular Filtration Rate (GFR), and Body Mass Index (BMI). PATIENTS AND METHODS: The study included 156 SCD subjects. Serum Creatinine (mg/dl) and Urea (mg/dl) as well as Microalbuminuria (mg/l) level were measured by using Biosystems kit (Biosystems, Barcelona, Spain) and Mindary BA88A semi-automated biochemistry analyzer. Glomerular filtration rate and body mass index were calculated by equations. Blood DNA extraction was achieved by using the modified G-DEX™IIb Genomic DNA Extraction Kit protocol. The PCR was done for the detection of the APOL1 G2 rs60910145 alleles by using allele-specific PCR and primers. RESULTS: The CC allele was more frequent in study cases (66.7%) than TT allele. The frequency of a mutated allele (CC) was insignificantly higher in males (67.8%) than in females (65.2%) and in rural (70.9%) than urban areas. It is also higher in Shankhab compared to other tribes and subjects 26-37 years compared to other, P˃0.05. Interstingly, the subjects who carry the CC allele showed a significantly higher level of Microalbuminuria, Creatinine, BMI, and Urea compared to those carry TT allele. Moreover, GFR is also higher in subjects who carry CC than TT allele but it is not significant. CONCULSION: Altogether, the study findings highlighted the link of normal and mutated APOL1 G2 rs60910145 alleles with SCD and displayed the significant value of mutated APOL1 allele in the prediction of early nephropathy in SCD patients.

Identification of natural antimicrobial peptides mimetic to inhibit Ca2+ influx DDX3X activity for blocking dengue viral infectivity.

Viruses are microscopic biological entities that can quickly invade and multiply in a living organism. Each year, over 36,000 people die and nearly 400 million are infected with the dengue virus (DENV). Despite dengue being an endemic disease, no targeted and effective antiviral peptide resource is available against the dengue species. Antiviral peptides (AVPs) have shown tremendous ability to fight against different viruses. Accelerating antiviral drug discovery is crucial, particularly for RNA viruses. DDX3X, a vital cell component, supports viral translation and interacts with TRPV4, regulating viral RNA metabolism and infectivity. Its diverse signaling pathway makes it a potential therapeutic target. Our study focuses on inhibiting viral RNA translation by blocking the activity of the target gene and the TRPV4-mediated Ca2+ cation channel. Six major proteins from camel milk were first extracted and split with the enzyme pepsin. The antiviral properties were then analyzed using online bioinformatics programs, including AVPpred, Meta-iAVP, AMPfun, and ENNAVIA. The stability of the complex was assessed using MD simulation, MM/GBSA, and principal component analysis. Cytotoxicity evaluations were conducted using COPid and ToxinPred. The top ten AVPs, determined by optimal scores, were selected and saved for docking studies with the GalaxyPepDock tools. Bioinformatics analyses revealed that the peptides had very short hydrogen bond distances (1.8 to 3.6 Å) near the active site of the target protein. Approximately 76% of the peptide residues were 5-11 amino acids long. Additionally, the identified peptide candidates exhibited desirable properties for potential therapeutic agents, including a net positive charge, moderate toxicity, hydrophilicity, and selectivity. In conclusion, this computational study provides promising insights for discovering peptide-based therapeutic agents against DENV.

Genomic characterization of extended spectrum beta lactamases producing multidrug-resistant Escherichia coli clinically isolated harboring chromosomally mediated CTX-M-15 from Alkharj, KSA.

Extended Spectrum Beta Lactamases (ESBLs) are the most prevalent enzymes conferring resistance to beta-lactams encoded on plasmids and rarely in chromosomes. This genomic study aims to characterize Escherichia coli to identify antimicrobial resistance genes (ARG), virulence factors, and phylogenetic relationships among ESBL-positive and negative isolates of E. coli obtained from Al-Kharj, Riyadh region, Saudi Arabia. Three clinical isolates from urine and vaginal swabs were obtained and subjected to whole genome sequencing, minimum inhibitory concentration, and antibiotic sensitivity tests. The pathogenicity and ARG were discovered, and the raw genomic sequences were assembled and annotated. Two isolates (E5 and E15) were MDR and ESBLs producers; the sequence type (ST) for E5 was 58, while those for E15 and E21 were 106. Most of the virulence genes were detected as plasmid-mediated; E21 was identified with a hyper-virulent plasmid (pH 2332-166) carrying different virulence factors (TraJ, traT, iss, etsC, hlyF, and iron acquisition associated proteins), plasmids (IncFII, IncFIB, and IncFIA), and insertion sequences (ISEc31). While most of the antimicrobial resistance genes were chromosomally mediated, a rare chromosome insertion of qnrS1 and blaCTX-M-15 with co-occurrence of Tn2 and ISKpn19 was identified in the E5 isolate. The consistent preservation of these genetic elements on bacterial chromosomes and plasmids could enhance the spread of Multidrug-Resistant (MDR) strains across various Enterobacteriaceae Species. This poses a significant threat to the effectiveness of existing antimicrobial treatments.

Identification and molecular docking of novel chikungunya virus NSP4 inhibitory peptides from camel milk proteins.

The chikungunya (CHIK) virus is an arbovirus belonging to the alphavirus (Togaviridae family). Around 85% of infected individuals suffer from symptoms such as high fever and severe joint pain; about 30 to 40% will develop a chronic joint illness. The Nsp4 protease is the most conserved protein in the alphavirus family and serves as an RNA-dependent RNA polymerase (RdRp). Targeting this enzyme might inhibit the CHIKV replication cycle. This work aims to in silico study the CHIKV RdRp inhibitory effect of peptides derived from camel milk protein as antiviral peptides. Various bioinformatics tools were recruited to identify, screen, predict and assess peptides obtained from camel milk as antiviral peptides (AVPs). During this study, CHIKV Nsp4 (polymerase) was used as a target to be inhibited by interaction with peptides derived from camel milk protein. Among 91 putative bioactive peptides, the best predicted 5 were further evaluated. Molecular docking showed that the top 5 AVPs generated better docking scores and interacted well with active sites of Nsp4 by the formation of different hydrogen bonds as well as other bonds. AVP63 and AVP20 showed the best Molecular docking and MD simulation results. The residue 315ASP of the GDD motif (catalytic core) exhibited a favorable interaction with the AVPs. The findings of this study suggest that the AVP20 derived from camel milk protein can be a potential novel CHIKV polymerase inhibitor.Communicated by Ramaswamy H. Sarma.

Acemannan ameliorates STZ-activated diabetes by attenuating high glucose via inhibiting inflammatory cytokines and apoptosis pathway.

Acemannan, the main polysaccharide in Aloe vera, is a -(1, 4)-acetylated polymannose. According to numerous research findings, acemannan is a viable alternative for the treatment of pathological disorders. Streptozotocin (STZ, 60 mg/kg) administered intraperitoneally caused type 2 diabetes in rats. The current study sought to determine the anti-diabetic efficacy of acemannan (25 and 50 mg/kg) in STZ-injected rats. Different biochemical parameters including HbA1C, glucose and serum insulin, lipid profile, inflammatory markers, antioxidant, oxidative balance, liver function test, glycogen and creatinine, and caspase-3 were evaluated. In addition, a molecular docking study was performed to estimate acemannan's binding affinity to inflammatory markers. Acemannan may be a potent anti-diabetic agent for the treatment of diabetic patients, which will aid in future research into alternative diabetes medications.

Antibiotic Susceptibility Profiling of Human Pathogenic Staphylococcus aureus Strains Using Whole Genome Sequencing and Genome-Scale Annotation Approaches.

Staphylococcus species are major pathogens with increasing importance due to the rise in antibiotic resistance. Whole genome sequencing and genome-scale annotation are promising approaches to study the pathogenicity and dissemination of virulence factors in nosocomial methicillin-resistant and multidrug-resistant bacteria in intensive care units. Draft genome sequences of eight clinical S. aureus strains were assembled and annotated for the prediction of antimicrobial resistance genes, virulence factors, and phylogenetic analysis. Most of the studied S. aureus strains displayed multi-resistance toward the tested drugs, reaching more than seven drugs up to 12 in isolate S22. The mecA gene was detected in three isolates (S14, S21, and S23), mecC was identified in S8 and S9, and blaZ was commonly identified in all isolates except strain S23. Additionally, two complete mobile genomic islands coding for methicillin resistance SCCmec Iva (2B) were identified in strains S21 and S23. Numerous antimicrobial resistance genes (norA, norC, MgrA, tet(45), APH(3')-IIIa, and AAC(6')-APH(2″)) were identified in chromosomes of different strains. Plasmid analysis revealed the presence of blaZ, tetK, and ermC in different plasmid types, located in gene cassettes containing plasmid replicons (rep) and insertion sequences (IS). Additionally, the aminoglycoside-resistant determinants were identified in S1 (APH(3')-IIIa), while AAC(6)-APH(2″) was detected in strains S8 and S14. The trimethoprim (dfrC) resistance gene was detected in S. aureus S21, and the fosfomycin (fosB) resistance gene was detected only in S. aureus S14. We also noted that S. aureus S1 belongs to ST1-t127, which has been reported as one of the most frequent human pathogen types. Additionally, we noted the presence of rare plasmid-mediated mecC-MRSA in some of our isolates.

Comparative Genomic Analysis of Multi-Drug Resistant Pseudomonas aeruginosa Sequence Type 235 Isolated from Sudan.

Pseudomonas aeruginosa (P. aeruginosa) is known to be associated with resistance to practically all known antibiotics. This is a cross-sectional, descriptive, laboratory-based analytical study in which 200 P. aeruginosa clinical isolates were involved. The DNA of the most resistant isolate was extracted and its whole genome was sequenced, assembled, annotated, and announced, strain typing was ascribed, and it was subjected to comparative genomic analysis with two susceptible strains. The rate of resistance was 77.89%, 25.13%, 21.61%, 18.09%, 5.53%, and 4.52% for piperacillin, gentamicin, ciprofloxacin, ceftazidime, meropenem, and polymyxin B, respectively. Eighteen percent (36) of the tested isolates exhibited a MDR phenotype. The most MDR strain belonged to epidemic sequence type 235. Comparative genomic analysis of the MDR strain (GenBank: MVDK00000000) with two susceptible strains revealed that the core genes were shared by the three genomes but there were accessory genes that were strain-specific, and this MDR genome had a low CG% (64.6%) content. A prophage sequence and one plasmid were detected in the MDR genome, but amazingly, it contained no resistant genes for drugs with antipseudomonal activity and there was no resistant island. In addition, 67 resistant genes were detected, 19 of them were found only in the MDR genome and 48 genes were efflux pumps, and a novel deleterious point mutation (D87G) was detected in the gyrA gene. The novel deleterious mutation in the gyrA gene (D87G) is a known position behind quinolone resistance. Our findings emphasize the importance of adoption of infection control strategies to prevent dissemination of MDR isolates.

Detection and characterization of the most common foodborne pathogens by using multiplex PCR procedure.

Food Microbial contamination is one of the most serious problems. A large percentage of food-borne illnesses are caused by food-borne pathogens, and diarrheal agents comprise more than half of the overall prevalence of food-borne illnesses in the globe, and more commonly in developing countries. This study aimed to identify the most-common foodborne organisms from foods in Khartoum state by PCR. A total of 207 food samples (raw milk, fresh cheese, yogurt, fish, sausage, mortadella, and eggs) were collected. DNA was extracted from food samples by guanidine chloride protocol, and then species-specific primers were used to identify Escherichia coli O157: H7, Listeria monocytogenes, Salmonella spp., Vibrio cholerae, V. parahaemolyticus, and Staphylococcus aureus. Out of 207 samples, five (2.41%) were positive for L. monocytogenes, one (0.48%) was positive for S. aureus, and one (0.48%) was positive for both Vibrio cholerae and Vibrio parahaemolyticus. From 91 fresh cheese samples, 2 (2.19%) were positive for L. monocytogenes, and one (1.1%) sample was positive for two different foodborne pathogens (V. cholerae and V. parahaemolyticus). Out of 43 Cow's milk samples, three (7%) samples were positive for L. monocytogenes, and out of 4 sausage samples, one (25 %) was positive for S. aureus. Our study revealed the presence of L. monocytogenes and V. cholera in raw milk and fresh cheese samples. Their presence is considered a potential problem and needs intensive hygiene efforts and standard safety measures before, during, and after food processing operations.

In silico molecular study of hepatitis B virus X protein as a therapeutic target.

The Hepatitis B virus is a leading cause of liver cirrhosis and hepatocellular carcinoma. HBx viral protein is considered a contributor to pathogenesis and hepatocarcinogenesis. This study aimed to screen the effect of some antiviral compounds to target HBx protein for inhibition of its function. Here, molecular docking, molcular dynsmic simulation, MM/GBSA and T-SNE methods were applied to study the complex stability and to cluster the conformations that generated in the simulation. Among the 179 compounds screened in this study, three antiviral agents (SC75741, Punicalagin, and Ledipasvir) exhibited the lowest docking energy and best interaction. Among these compounds, SC75741 was identified as a potent inhibitor of HBx that showed the best and most stable interaction during molecular dynamic simulation, and blocking a region near to HBx helix resides (aa 88-100) that is associated with cell invasion. The analysis of relative binding free energy through MM/GBSA for molecular dynamic simulation results revealed binding energy -9.9 kcal/mol for SC75741, -11 kcal/mol for Punicalagin, and -10.1 kcal/mol for Ledipasvir. These results elucidate the possible use of these compounds in the research for targeting HBx.Communicated by Ramaswamy H. Sarma.

The First Genomic Characterization of the Chikungunya Virus in Saudi Arabia.

BACKGROUND: Chikungunya is an arboviral infection caused by the Chikungunya virus (CHIKV) transmitted to humans by mosquitoes of Aedes spp. CHIKV has been confined to African countries and South-East Asia up to 2004, but since then, the pathogen has become more global, and its high morbidity rate has become more visible. Saudi Arabia is not an endemic region of CHIKV, and the virus's origin is not yet fully understood. This study aimed to characterize the genome of CHIKV from samples detected in Jeddah in 2018. METHOD: Twenty-two sets of primers were designed to amplify near-full length genome of CHIKV. RT-PCR was conducted from clinical samples. Two samples were used for studying near complete genome sequence while the remaining samples were used to study the E1 gene. Different bioinformatics tools were utilized. RESULTS: Phylogenetic analysis showed that the CHIKV strains clustered with strains isolated from Kenya during 2017-2018 and belonged to ECSA genotype. E1: L136F, K211E and I317V mutations were identified in our strains. Also, E2: M74I, A76T, and V264A mutations were documented. Additionally, the capsid N79S substitution was also detected. CONCLUSION: The genome of CHIKV was analyzed for the first time in Saudi Arabia to better understand the origin of the CHIKV and its genetic diversity, which showed high similarity with IE-a subclade of CHIKV strains detected in Mombasa (Kenya) indicating its possible origin.

Phytochemical analysis and nephroprotective potential of Ajwa date in doxorubicin-induced nephrotoxicity rats: Biochemical and molecular docking approaches.

The purpose of this study is to evaluate the likely defensive impact of Ajwa date aqueous extract (AJDAE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. Sixty male Wister albino rats were randomly and equally separated into six groups (n = 10), and they were treated as follows: untreated control group, extract groups administered with 0.75 and 1.5 mg kg bw of AJDAE, toxicant control group administered with DOX, and prophylactic groups were treated with 0.75 and 1.5 mg/kg of AJDAE and 15 mg/kg DOX. Biochemical parameters, antioxidant enzymes, renal functions, DNA integrity, and histopathology were studied to evaluate the nephroprotective activity of AJDAE. Furthermore, bioactive compounds were utilized for in silico molecular docking. AJDAE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, calcium, phosphorous, and uric acid), antioxidative markers, and MDA. Noticeable histopathological improvements supported this result. Results of in silico studies revealed that d-Mannitol, 6TMS derivative, palmitic acid, and TMS derivative had a higher docking score with human soluble epoxide hydrolase (-10.9 kcal/mol) and NF-κB-DNA (-7 kcal/mol). The present findings indicated that AJDAE could decrease ROS generation and lipid peroxidation (LPO) and repair the DOX injection-related DNA damage.

Klebsiella pneumonia in Sudan: Multidrug Resistance, Polyclonal Dissemination, and Virulence.

The emergence and global expansion of hyper-virulent and multidrug resistant (MDR) Klebsiella pneumoniae is an increasing healthcare threat worldwide. The epidemiology of MDR K. pneumoniae is under-characterized in many parts of the world, particularly Africa. In this study, K. pneumoniae isolates from hospitals in Khartoum, Sudan, have been whole-genome sequenced to investigate their molecular epidemiology, virulence, and resistome profiles. Eighty-six K. pneumoniae were recovered from patients in five hospitals in Khartoum between 2016 and 2020. Antimicrobial susceptibility was performed by disk-diffusion and broth microdilution. All isolates underwent whole genome sequencing using Illumina MiSeq; cgMLST was determined using Ridom SeqSphere+, and 7-loci MLST virulence genes and resistomes were identified. MDR was observed at 80%, with 35 isolates (41%) confirmed carbapenem-resistant. Thirty-seven sequence types were identified, and 14 transmission clusters (TC). Five of these TCs involved more than one hospital. Ybt9 was the most common virulence gene detected, in addition to some isolates harbouring iuc and rmp1. There is a diverse population of K. pneumoniae in Khartoum hospitals, harbouring multiple resistance genes, including genes coding for ESBLs, carbapenemases, and aminoglycoside-modifying enzymes, across multiple ST's. The majority of isolates were singletons and transmissions were rare.

Enhanced textile dye removal from wastewater using natural biosorbent and Shewanella algae B29: Application of Box Behnken design and genomic approach.

In this study, Box-Behnken design combining seven factors at three levels were used to optimize the elimination of CI Reactive Red 66 in artificial seawater, by the combination of eco-friendly bio-sorbents and acclimated halotolerant microbial strain. Results showed that macro-algae and cuttlebone (2 %) were the best natural bio-sorbent. Additionally, the selected halotolerant strain able to rapidly remove dye was identified as Shewanella algae B29. The optimization process revealed that decolourization of CI Reactive Red 66 yields reached 91.04 % under the following variable values: dyes concentration (100 mg/l), salinity (30 g/l), peptone (2 %), pH (5), algae C (3 %), cuttlebone (1.5 %) and agitation (150 rpm). The whole genome analysis of S. algae B29 demonstrated the presence of several genes coding for valuable enzymes involved in textile dyes biotransformation, adaptation to stress as well as biofilm formation implying its potential use in biological textile wastewater treatment.

Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1.

Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of -10.4, -10.1, and -9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.

Sterubin protects against chemically-induced Alzheimer's disease by reducing biomarkers of inflammation- IL-6/ IL-ß/ TNF-α and oxidative stress- SOD/MDA in rats.

Sterubin, a flavanone is an active chemical compound that possesses neuroprotective activity. The current investigation was intended to assess the sterubin effect in scopolamine-activated Alzheimer's disease. The rats were induced with scopolamine (1.5 mg/kg) followed by treatment with sterubin (10 mg/kg) for 14 days. Behavioural analysis was predictable by the Y-maze test and Morris water test. Biochemical variables like nitric oxide acetylcholinesterase, Choline acetyltransferase, antioxidant markers like superoxide dismutase, glutathione transferase, malondialdehyde, catalase, and myeloperoxidase activity, neuroinflammatory markers such as tumor necrosis factor-alpha, nuclear factor kappa B, interferon-gamma, interleukin (IL-1ß), and IL-6 were measured. The result stated that sterubin reversed the oxidative stress parameters, increased motor performance, and lowered the inflammatory markers in scopolamine-induced rats. The study demonstrated that sterubin possesses neuroprotective, anti-inflammatory, and antioxidant properties which can be used as a beneficial medication in AD.

In silico screening of the effectiveness of natural compounds from algae as SARS-CoV-2 inhibitors: molecular docking, ADMT profile and molecular dynamic studies.

Marine species are known as rich sources of metabolites largely involved in the pharmaceutical industry. This study aimed to evaluate in silico the effect of natural compounds identified in algae on the SARS-CoV-2 Main protease, RNA-dependent-RNA polymerase activity (RdRp), endoribonuclease (NSP15) as well as on their interaction with viral spike protein. A total of 45 natural compounds were screened for their possible interaction on SARS-CoV-2 target proteins using Maestro interface for molecular docking, molecular dynamic (MD) simulation to estimate compounds binding affinities. Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4'-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein). The complex of the main protease with laminarin shows the most stable RMSD during a 150 ns MD simulation time. Which indicates their possible inhibitory activity on SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Engineering processive cellulase of Clostridium thermocellum to divulge the role of the carbohydrate-binding module.

The processive cellulase (CelO) is an important modular enzyme of Clostridium thermocellum. To study the effect of the carbohydrate-binding module (CBM3b) on the catalytic domain of CelO (GH5), four engineered derivatives of CelO were designed by truncation and terminal fusion of CBM3b. These are CBM at the N-terminus, native form (CelO-BC, 62 kDa); catalytic domain only (CelO-C, 42 kDa); CBM at the C-terminus (CelO-CB, 54 kDa) and CBM attached at both termini (CelO-BCB, 73 kDa). All constructs were cloned into pET22b (+) and expressed in Escherichia coli BL21 (DE3) star. The expression levels of CelO-C, CelO-CB, CelO-BC, and CelO-BCB were 35%, 35%, 30%, and 20%, respectively. The enzyme activities of CelO-C, CelO-CB, CelO-BC, and CelO-BCB against 1% regenerated amorphous cellulose (RAC) were 860, 758, 985, and 1208 units per µmole of the enzyme, respectively. The enzymes were partially purified from the lysate of E. coli cells by heat treatment followed by anion exchange FPLC purification. Against RAC, CelO-C, CelO-CB, CelO-BC, and CelO-BCB showed KM values of 32, 33, 45, and 43 mg⋅mL-1 and Vmax values of 3571, 3846, 3571, and 4545 U⋅min-1 , respectively. CBM3b at the N-terminus of GH5 linked through a P/T-rich linker was found to enhance the catalytic activity and thermostability of the enzyme.