Functional analysis and comparative genomics of Rahnella perminowiae S11P1 and Variovorax sp. S12S4, two plant growth-promoting rhizobacteria isolated from Crocus sativus L. (saffron) rhizosphere.

BACKGROUND: Rahnella perminowiae S11P1 and Variovorax sp. S12S4 are two plant growth-promoting rhizobacteria that were previously isolated from the rhizosphere of Crocus sativus L. (saffron), and have demonstrated interesting PGP activities and promising results when used as inoculants in field trials. To further elucidate the molecular mechanisms underlying their beneficial effects on plant growth, comprehensive genome mining of S11P1 and S12S4 and comparative genomic analysis with closely related strains were conducted. RESULTS: Functional annotation of the two strains predicted a large number of genes involved in auxin and siderophore production, nitrogen fixation, sulfur metabolism, organic acid biosynthesis, pyrroloquinoline quinone production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, volatile organic compounds production, and polyamine biosynthesis. In addition, numerous genes implicated in plant-bacteria interactions, such as those involved in chemotaxis and quorum sensing, were predicted. Moreover, the two strains carried genes involved in bacterial fitness under abiotic stress conditions. Comparative genomic analysis revealed an open pan-genomic structure for the two strains. COG annotation showed that higher fractions of core and accessory genes were involved in the metabolism and transport of carbohydrates and amino acids, suggesting the metabolic versatility of the two strains as effective rhizosphere colonizers. Furthermore, this study reports the first comparison of Multilocus sequence analysis (MLSA) and core-based phylogenies of the Rahnella and Variovorax genera. CONCLUSIONS: The present study unveils the molecular mechanisms underlying plant growth promotion and biocontrol activity of S11P1 and S12S4, and provides a basis for their further biotechnological application in agriculture.

Unveiling Blastocystis epidemiology in Morocco: subtype diversity among clinical patients with and without gastrointestinal manifestations in the Meknes region.

Blastocystis is an intestinal protist frequently identified in humans and other animals, though its clinical significance remains controversial. This study aimed to determine the prevalence and genetic diversity of Blastocystis in faecal samples from symptomatic (n = 55) and asymptomatic (n = 50) individuals seeking medical care in Meknes, Morocco. Detection of the protist was accomplished through coproparasitological examination and culture in Jones medium. Culture-positive samples were subjected to molecular analyses (PCR and Sanger sequencing) based on sequences of the small subunit ribosomal RNA gene. Epidemiological questionnaires on demographics and potential risk factors were collected from participating patients. The overall Blastocystis infection rate was 51.4% (54/105), with no differences between symptomatic (52.7%, 29/55) and asymptomatic (50.0%, 25/50) individuals. Sequence analyses identified three Blastocystis subtypes, with ST3 being the most prevalent (42.0%), followed by ST1 (34.0%), and ST2 (12.0%). Regarding intra-subtype diversity, allele 4 was found within ST1; alleles 11/12 and alleles 34/36 (alone or in combination) were identified within ST2 and ST3 respectively. Allele 34 in ST3 (40.8%) and allele 4 in ST1 (34.7%) were the most common genetic variants circulating in the surveyed clinical population. A statistically significant association between ST2 and the presence of flatulence was observed. This is the first study assessing the epidemiology and genetic diversity of Blastocystis sp. in the Meknes region, Morocco.

Genomic analysis of Paenibacillus sp. MDMC362 from the Merzouga desert leads to the identification of a potentially thermostable catalase.

Microorganisms in hot deserts face heat and other environmental conditions, such as desiccation, UV radiation, or low nutrient availability. Therefore, this hostile environment harbour microorganisms with acquired characteristics related to survival in their habitat, which can be exploited in biotechnology. In this work, the genome of Paenibacillus sp. MDMC362 isolated from the Merzouga desert in Morocco was sequenced to understand its survival strategy's genetic basis; and to evaluate the thermostability of a catalase extracted from genomic annotation files using molecular dynamics. Paenibacillus sp. MDMC362 genome was rich in genetic elements involved in the fight against different stresses, notably temperature stress, UV radiations, osmotic stress, carbon starvation, and oxidative stress. Indeed, we could identify genes of the operons groES-groEL and hrcA-grpE-dnaK and those involved in the different stages of sporulation, which can help the bacteria to survive the high temperatures imposed by a desertic environment. We also observed the genetic components of the UvrABC system and additional mechanisms involved in DNA repair, which help overcome UV radiation damage. Other genes have been identified in the genome, like those coding for ectoine and proline, that aids fight osmotic stress and desiccation. Catalase thermostability investigation using molecular dynamics showed that the protein reached stability and conserved its compactness at temperatures up to 373.15 K. These results suggest a potential thermostability of the enzyme. Since the studied protein is a core protein, thermostability could be conserved among Paenibacillus sp. MDMC362 closely related strains; however, bacteria from harsh environments may have a slight advantage regarding protein stability.

Virtual docking screening and quantitative structure-activity relationship studies to explore AKT and PI3K inhibitors acting on mTOR in cancers by theoretical biology and medical modeling.

Introduction: The mechanistic target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells with a central role in the regulation of many fundamental cellular processes. It is strongly connected to phosphatidylinositol 3-kinase (PI3K) and AKT signaling. Activation of the PI3K/AKT/mTOR pathway leads to a profound disruption in the control of cell growth and survival, which ultimately leads to competitive growth advantage, metastatic competence, angiogenesis and therapeutic resistance. Material and methods: To explore the common competitive adenosine triphosphate (ATP) inhibitors PI3K/AKT and PI3K/mTOR, we built a 2D mTOR-SAR model that predicted the bioactivity of AKT and PI3K inhibitors towards mTOR. The interaction of the best inhibitors was evaluated by docking analysis and compared to that of the standard AZ8055 and XL388 inhibitors. Results: A mechanistic target of rapamycin-quantitative structure-activity relationship (mTOR-QSAR) model with a correlation coefficient (R2) of 0.80813 and a root mean square error of 0.17756 was obtained, validated and evaluated by a cross-validation leave-one-out method. The best predicted AKT and PI3K inhibitor pIC50 activities were 9.36-9.95 and 9.23-9.87 respectively. Conclusions: After docking and several comparisons, the inhibitors with better predictions showed better affinity and interaction with mTOR compared to AZ8055 and XL388, so we have found that 2 AKT inhibitors and 9 mTOR inhibitors met the Lipinski and Veber criteria and could be future drugs.

Genomic analysis of two Bacillus safensis isolated from Merzouga desert reveals desert adaptive and potential plant growth-promoting traits.

Deserts represent extreme environments for microorganisms, and conditions such as high soil salinity, nutrient deficiency, and increased levels of UV radiation make desert soil communities of high biotechnological potential. In this study, we isolated, sequenced, and assembled the genomes of Bacillus safensis strains BcP62 and Bcs93, to which we performed comparative genome analyses. Using the DDH and ANI of both strains with the available B. safensis genomes, we identified three potential subspecies within this group. Intra-species core genome phylogenetic analysis did not result in clustering genomes by niche type, with some exceptions. This study also revealed that the genomes of the analyzed strains possessed plant growth-promoting characteristics, most of which were conserved in all B. safensis strains. Furthermore, we highlight the genetic features of B. safensis BcP62 and Bcs93 related to survival in the Merzouga desert in Morocco. These strains could be potentially used in agriculture as PGPB in extreme environments, given their high tolerability to unfavorable conditions.

Variants of human CLDN9 cause mild to profound hearing loss.

Hereditary deafness is clinically and genetically heterogeneous. We investigated deafness segregating as a recessive trait in two families. Audiological examinations revealed an asymmetric mild to profound hearing loss with childhood or adolescent onset. Exome sequencing of probands identified a homozygous c.475G>A;p.(Glu159Lys) variant of CLDN9 (NM_020982.4) in one family and a homozygous c.370_372dupATC;p.(Ile124dup) CLDN9 variant in an affected individual of a second family. Claudin 9 (CLDN9) is an integral membrane protein and constituent of epithelial bicellular tight junctions (TJs) that form semipermeable, paracellular barriers between inner ear perilymphatic and endolymphatic compartments. Computational structural modeling predicts that substitution of a lysine for glutamic acid p.(Glu159Lys) alters one of two cis-interactions between CLDN9 protomers. The p.(Ile124dup) variant is predicted to locally misfold CLDN9 and mCherry tagged p.(Ile124dup) CLDN9 is not targeted to the HeLa cell membrane. In situ hybridization shows that mouse Cldn9 expression increases from embryonic to postnatal development and persists in adult inner ears coinciding with prominent CLDN9 immunoreactivity in TJs of epithelia outlining the scala media. Together with the Cldn9 deaf mouse and a homozygous frameshift of CLDN9 previously associated with deafness, the two bi-allelic variants of CLDN9 described here point to CLDN9 as a bona fide human deafness gene.

Creaming behavior prediction of argan oil in water emulsion stabilized by lacto-fermentation: creaming index.

BACKGROUND: In order to improve the taste acceptability of certain nutritional oils, it has been decided in this study to introduce them in an emulsion whose surfactant is casein, then to carry out a lacto-fermentation, leading to a dairy-like product with added nutritional value and health benefit. In this context, a plan of mixtures has been proposed for the preparation of emulsions based on argan oil, sodium caseinate and starch, with concentrations ranged between (10-20%) and (0-2%) and (0-1.5%) respectively. All emulsions were homogenized at two high stirring velocities (10,000-20,000 rpm) and two stirring times (5-20 min). The physical stability was assessed by visual analysis and microstructural measurements. The Creaming index was calculated for selected emulsions to predict their creaming behavior. RESULTS: All emulsions showed a creaming behavior except one emulsion that required the highest values of all factors, which showed the highest creaming index with an average particle size of 11.27 µm. The absence or the variation of one or all factors led to various degrees of instabilities verified in all other emulsions. Due to the synergistic action of all parameters, the emulsion stability was attributed to the reduction of droplets size, the increase of continuous phase viscosity and the decrease of coalescence. CONCLUSION: The parameters that played a major role in the stability of the emulsion consists of: stirring velocity and time, sodium caseinate/oil ratio and starch/sodium caseinate ratio. The underlying structure and the interaction of the fluid droplets within the solid like product is what holds the stability of the product against settling or separation during fermentation.

Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing.

BACKGROUND: Large-scale human sequencing projects have described around a hundred-million single nucleotide variants (SNVs). These studies have predominately involved individuals with European ancestry despite the fact that genetic diversity is expected to be highest in Africa where Homo sapiens evolved and has maintained a large population for the longest time. The African Genome Variation Project examined several African populations but these were all located south of the Sahara. Morocco is on the northwest coast of Africa and mostly lies north of the Sahara, which makes it very attractive for studying genetic diversity. The ancestry of present-day Moroccans is unknown and may be substantially different from Africans found South of the Sahara desert, Recent genomic data of Taforalt individuals in Eastern Morocco revealed 15,000-year-old modern humans and suggested that North African individuals may be genetically distinct from previously studied African populations. RESULTS: We present SNVs discovered by whole genome sequencing (WGS) of three Moroccans. From a total of 5.9 million SNVs detected, over 200,000 were not identified by 1000G and were not in the extensive gnomAD database. We summarise the SNVs by genomic position, type of sequence gene context and effect on proteins encoded by the sequence. Analysis of the overall genomic information of the Moroccan individuals to individuals from 1000G supports the Moroccan population being distinct from both sub-Saharan African and European populations. CONCLUSIONS: We conclude that Moroccan samples are genetically distinct and lie in the middle of the previously observed cline between populations of European and African ancestry. WGS of Moroccan individuals can identify a large number of novel SNVs and aid in functional characterisation of the genome.

Virtual docking screening and QSAR studies to explore AKT and mTOR inhibitors acting on PI3K in cancers.

The phosphoinositide 3-kinase (PI3K) pathway is an important regulator of cell proliferation and metabolism. PI3K activation initiates a signal transduction cascade, of which the major effectors are the kinases AKT and mTOR. Aberrant activation of the PI3K/AKT/mTOR pathway is frequently observed in many human malignancies and the combination of compounds simultaneously targeting different related molecules in the PI3K/AKT/mTOR pathway leads to synergistic activity. To explore the competing common ATP inhibitors PI3K/AKT and PI3K/mTOR we developed a model PI3K-SAR 2D which made it possible to predict the bioactivity of inhibitors of AKT and mTOR towards PI3K; the interaction of the best inhibitors was evaluated by docking analysis and compared to that of dactolisib and pictilisib. A PI3K-SAR model with a correlation coefficient (R2) of 0.81706 and an RMSE of 0.16029 was obtained, which was validated and evaluated by a cross-validation method, LOO. The most predicted AKT and mTOR inhibitors present respectively pIC50 activities between 9.26-9.93 and 9.59-9.87. After docking and several comparisons, inhibitors with better predictions showed better affinity and interaction with PI3K compared to pictilisib and dactolisib, so we found that 4 inhibitors of AKT and 14 mTOR inhibitors met the criteria of Lipinski and Veber and could be future drugs.

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa.

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Syneresis investigations of lacto-fermented sodium caseinate in a mixed model system.

BACKGROUND: The textural characteristics of fermented dairy products are important quality parameters that play a major role in their stability and consumer's acceptance. The aim of this study was to investigate the influence of sodium caseinate, starch, lactose and lactic acid bacteria as ferment on the syneresis in a mixed model system, and to evaluate their impact on the acid gel formation throughout pH and zeta potential monitoring. Accordingly, a protocol was designed to perform an experimental design by using a mixture of the selected factors. RESULTS: A significant decrease of syneresis was detected in all mixtures at 8% of sodium caseinate, ranging between a minimum of 1.8% and a maximum of 20.6% compared to the mixtures at 3% of sodium caseinate in which the syneresis decrease had ranged between a minimum of 22.2% and a maximum of 47.8%. The addition of starch had a significant impact on the acidification profile and on the syneresis of the fermented mixed model. Moreover, the monitoring of pH and zeta potential during the lacto-fermentation process has also led to a better understanding of the acid gelation and the syneresis variations. CONCLUSION: Syneresis varies very closely with sodium caseinate concentration, starch concentration and also with their association, regardless of the concentrations of lactose and ferment. In fact syneresis could be reduced to an optimum level if a sodium caseinate-starch mixed system is employed: Less syneresis gels could be obtained at a sodium caseinate concentration above 5% if starch is used above 1%.

The displacement study of 99m Tc-DTPA-Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking.

The 99m Tc-DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99m Tc-DTPA have never been characterized. This study will cover in vitro the binding rates of 99m Tc-DTPA on HSA and the 99m Tc-DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99m Tc-DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99m Tc-DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99m Tc-DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99m Tc-DTPA binding. 99m Tc-DTPA could bind to human serum albumin in many locations in site I and I-II, but strongly bound to site I through hydrogen bonds.

Consumption of Argan Oil Improves Anti-Oxidant and Lipid Status in Hemodialysis Patients.

OBJECTIVE: Virgin Argan oil (VAO) is of interest in oxidative stress and lipid profile because of its fat composition and antioxidant compounds. We investigated the effect of VAO consumption on lipid profile and antioxidant status in hemodialysis patients after a 4-week period of consumption. METHODS: In a crossover, controlled trial, 37 patients (18 men, 19 women) with end-stage renal disease on maintenance hemodialysis, were randomly assigned to a 4-week VAO diet. Fasting plasma lipids, vitamin E and oxidized LDL (ox-LDL) were analyzed. Malondialdehyde (MDA) was determined before and after hemodialysis session. RESULTS: There was no significant change in serum total cholesterol and ox-LDL. However, VAO consumption decreased the levels of triglyceride (p = 0.03), total cholesterol (p = 0.02) and low-density lipoprotein (p = 0.03) and increased the levels of high-density lipoprotein (p = 0.01). Plasma vitamin E contents significantly increased from baseline only in VAO-group (p < 0.001). Hemodialysis session increased MDA levels, but the increase in VAO group was less than in control group. CONCLUSION: VAO consumption improved lipid profile and oxidative stress status in hemodialysis patients.

A Comprehensive Analysis of 3 Moroccan Genomes Revealed Contributions From Both African and European Ancestries.

Genetic variations in the human genome represent the differences in DNA sequence within individuals. This highlights the important role of whole human genome sequencing which has become the keystone for precision medicine and disease prediction. Morocco is an important hub for studying human population migration and mixing history. This study presents the analysis of 3 Moroccan genomes; the variant analysis revealed 6 379 606 single nucleotide variants (SNVs) and 1 050 577 small InDels. Of those identified SNVs, 219 152 were novel, with 1233 occurring in coding regions, and 5580 non-synonymous single nucleotide variants (nsSNP) variants were predicted to affect protein functions. The InDels produced 1055 coding variants and 454 non-3n length variants, and their size ranged from -49 and 49 bp. We further analysed the gene pathways of 8 novel coding variants found in the 3 genomes and revealed 5 genes involved in various diseases and biological pathways. We found that the Moroccan genomes share 92.78% of African ancestry, and 92.86% of Non-Finnish European ancestry, according to the gnomAD database. Then, population structure inference, by admixture analysis and network-based approach, revealed that the studied genomes form a mixed population structure, highlighting the increased genetic diversity in Morocco.

Targeting decaprenylphosphoryl-ß-D-ribose 2'-epimerase for Innovative Drug Development Against Mycobacterium Tuberculosis Drug-Resistant Strains.

Tuberculosis (TB) remains a global health challenge with the emergence of drug-resistant Mycobacterium tuberculosis variants, necessitating innovative drug molecules. One potential target is the cell wall synthesis enzyme decaprenylphosphoryl-ß-D-ribose 2'-epimerase (DprE1), crucial for virulence and survival. This study employed virtual screening of 111 Protein Data Bank (PDB) database molecules known for their inhibitory biological activity against DprE1 with known IC50 values. Six compounds, PubChem ID: 390820, 86287492, 155294899, 155522922, 162651615, and 162665075, exhibited promising attributes as drug candidates and validated against clinical trial inhibitors BTZ043, TBA-7371, PBTZ169, and OPC-167832. Concurrently, this research focused on DprE1 mutation effects using molecular dynamic simulations. Among the 10 mutations tested, C387N significantly influenced protein behavior, leading to structural alterations observed through root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent-accessible surface area (SASA) analysis. Ligand 2 (ID: 390820) emerged as a promising candidate through ligand-based pharmacophore analysis, displaying enhanced binding compared with reference inhibitors. Molecular dynamic simulations highlighted ligand 2's interaction with the C387N mutation, reducing fluctuations, augmenting hydrogen bonding, and influencing solvent accessibility. These collective findings emphasize ligand 2's efficacy, particularly against severe mutations, in enhancing protein-ligand complex stability. Integrated computational and pharmacophore methodologies offer valuable insights into drug candidates and their interactions within intricate protein environments. This research lays a strategic foundation for targeted interventions against drug-resistant TB, highlighting ligand 2's potential for advanced drug development strategies.

Temporal Dynamics and Genomic Landscape of SARS-CoV-2 After Four Years of Evolution.

Introduction Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive genomic evolution, impacting public health policies, diagnosis, medication, and vaccine development. This study leverages advanced bioinformatics to assess the virus's temporal and regional genomic evolution from December 2019 to October 2023. Methods Our analysis incorporates 16,575 complete SARS-CoV-2 sequences collected from 214 countries. These samples were comparatively analyzed, with a detailed characterization of nucleic mutations, lineages, distribution, and evolutionary patterns during each year, using the Wuhan-Hu-1 strain as the reference. Results Our analysis has identified a total of 21,580 mutations that we classified into transient mutations, which diminished over time, and persistent mutations with steadily increasing frequencies. This mutation landscape led to a notable surge in the evolutionary rate, rising from 13 mutations per sample in 2020 to 96 by 2023, with minor geographic variations. The phylogenetic analysis unveiled three distinct evolutionary branches, each representing unique viral evolution pathways. These lineages exhibited a tendency for a reduced duration of dominance with a shortening prevalence period over time, as dominant strains were consistently replaced by more fit variants. Notably, the emergence of the Alpha and Delta variants in 2021 was followed by the subsequent dominance of Omicron clade variants that have branched into several recombinant variants in 2022, marking a significant shift in the viral landscape. Conclusion This study sheds light on the dynamic nature of SARS-CoV-2 evolution, emphasizing the importance of continuous and vigilant genomic surveillance. The dominance of recombinant lineages, coupled with the disappearance of local variants, underscores the virus's adaptability.

Unraveling the Role of Neuroligin3 in Autism Spectrum Disorders: Pathophysiological Insights and Targeted Therapies.

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social and communication skills, repetitive behaviors, and/or restricted interests with a prevalence of as high as 1% of children. Autism spectrum has strongly associated with genetic factors and exhibits wide clinical and heterogeneous genetic architecture. Most genes associated with Autism are involved in neuronal and synaptic development. The neuroligin3, the sex-linked gene on the X chromosome, was the first gene to be associated with a monogenic form of Autism. Neuroligin3 is a postsynaptic cell adhesion protein involved in synapse transmission, brain formation, and neuronal development. In this review, we provide recent findings on different mutations in the Neuroligin3 gene linked to Autism spectrum disorder and their molecular pathway effect. We also give the behavioral, and synaptic alterations reported in the Neuroligin3 animal model of Autism and the potential therapeutic strategies targeting the biological processes and the main symptoms of autism spectrum disorder. In addition, we discuss the use of novel technologies like induced pluripotent stem cells from Autistic patients that have the potential to differentiate in human neurons and therefore have a variety of applications in therapy and biomedical studies to search specific biomarkers, and develop systems for screening chemical molecules in human cells to discover target therapies.

Genetic diversity and evolutionary dynamics of the Omicron variant of SARS-CoV-2 in Morocco.

Among the numerous variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that have been reported worldwide, the emergence of the Omicron variant has drastically changed the landscape of the coronavirus disease (COVID-19) pandemic. Here, we analyzed the genetic diversity of Moroccan SARS-CoV-2 genomes with a focus on Omicron variant after one year of its detection in Morocco in order to understand its genomic dynamics, features and its potential introduction sources. From 937 Omicron genomes, we identified a total of 999 non-unique mutations distributed across 92 Omicron lineages, of which 13 were specific to the country. Our findings suggest multiple introductory sources of the Omicron variant to Morocco. In addition, we found that four Omicron clades are more infectious in comparison to other Omicron clades. Remarkably, a clade of Omicron is particularly more transmissible and has become the dominant variant worldwide. Moreover, our assessment of Receptor-Binding Domain (RBD) mutations showed that the Spike K444T and N460K mutations enabled a clade higher ability of immune vaccine escape. In conclusion, our analysis highlights the unique genetic diversity of the Omicron variant in Moroccan SARS-CoV-2 genomes, with multiple introductory sources and the emergence of highly transmissible clades. The distinctiveness of the Moroccan strains compared to global ones underscores the importance of ongoing surveillance and understanding of local genomic dynamics for effective response strategies in the evolving COVID-19 pandemic.

Draft Genome Sequences of Four Plant Growth-Promoting Rhizobacteria Isolated from Saffron (Crocus sativus L.) Rhizosphere in Morocco.

We report the draft genome sequences of plant growth-promoting Rahnella perminowiae strain S11P1, Variovorax sp. strain S12S4, and Pseudomonas sp. strains S11A4 and S11P7, which were isolated from saffron (Crocus sativus L.) rhizosphere. Several genes were predicted to be involved in auxin production, phosphate solubilization, and other specialized functions in plant growth and defense.

Facing Antitubercular Resistance: Identification of Potential Direct Inhibitors Targeting InhA Enzyme and Generation of 3D-pharmacophore Model by in silico Approach.

Purpose: The enoyl-acyl carrier protein reductase (InhA) is one of the important key enzymes employed in mycolic acids biosynthesis pathway and an important component of mycobacterial cell walls. This enzyme has also been identified as major target of isoniazid drug, except that isoniazid needs to be activated first by the catalase peroxidase (KatG) protein to form the isonicotinoyl-NAD (INH-NAD) adduct that inhibits the action of InhA enzyme. However, this activation becomes more difficult and unreachable with the problem of mutation-related resistance caused mainly by acquired mutations in KatG and InhA protein. Our main interest in this study is to identify direct InhA inhibitors using computer-aided drug design. Methods: Computer-aided drug design was used to solve this problem by applying three different approaches including mutation impact modelling, virtual screening and 3D-pharmacophore search. Results: A total of 15 mutations were collected from the literature, then a 3D model was generated for each of them and their impact was predicted. Of the 15 mutations, 10 were found to be deleterious and have a direct effect on flexibility, stability and SASA of the protein. In virtual screening, from 1,000 similar INH-NAD analogues obtained by the similarity search method, 823 compounds passed toxicity filter and drug likeness rules, which were then docked to the wild-type of InhA protein. Subsequently, 34 compounds with binding energy score better than that of INH-NAD were selected and docked against the 10 generated mutated models of InhA. Only three leads showed a lower binding affinity better than the reference. The 3D-pharmacophore model approach was used to identify the common features between those three compounds by generating a pharmacophoric map. Conclusion: The result of this study may pave the way to develop more potent mutant-specific inhibitors to overcome this resistance.