SARS coronavirus (COVID-19) is a real health challenge of the 21^st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi -way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.

Background: Antimicrobial resistance became the leading cause of death globally, resulting in an urgent need for the discovery of new, safe, and efficient antibacterial agents. Compounds derived from plants can provide an essential source of new types of antibiotics. A. indica (neem) plant is rich in antimicrobial phytoconstituents. Here, we used the sensitive and reliable gas chromatography-mass spectrometry (GC–MS) approach, for the quantitative and quantitative determination of bioactive constituents in methanolic extract of neem leaves grown in Sudan. Subsequently, antibacterial activity, pharmacokinetic and toxicological properties were utilized using in silico tools. Results: The methanolic extract of neem leaves was found to have antibacterial activity against all pathogenic and reference strains. The lowest concentration reported with bacterial activity was 3.125%, which showed zones of inhibition of more than 10 mm on P. aeruginosa, K. pneumoniae, Citrobacter spp., and E. coli, and 8 mm on Proteus spp., E. faecalis, S. epidermidis, and the pathogenic S. aureus. GC–MS analysis revealed the presence of 30 chemical compounds, including fatty acids (11), hydrocarbons (9), pyridine derivatives (2), aldehydes (2), phenol group (1), aromatic substances (1), coumarins (1), and monoterpenes (1). In silico and in vitro tools revealed that.beta.d-Mannofuranoside, O-geranyl was the most active compound on different bacterial proteins. It showed the best docking energy (-8 kcal/mol) and best stability with different bacterial essential proteins during molecular dynamic (MD) simulation. It also had a good minimum inhibitory concentration (MIC) (32 μg/ml and 64 μg/ml) against S. aureus (ATCC 25,923) and E. coli (ATCC 25,922) respectively. Conclusion: The methanolic extract of A. indica leaves possessed strong antibacterial activity against different types of bacteria. Beta.d-Mannofuranoside, O-geranyl was the most active compound and it passed 5 rules of drug-likeness properties. It could therefore be further processed for animal testing and clinical trials for its possible use as an antibacterial agent with commercial values.

Waterborne Escherichia coli are a major reservoir of antimicrobial resistance (AMR). Carbapenem-resistance, especially when mediated by transferable carbapenemase-encoding genes, is spreading worldwide and causing dramatically limiting treatment options. In our country, studies for the detection of carbapenem resistance in drinking water do not exist; therefore, this work was carried out to determine the prevalence of carbapenem-resistant genes “bla_KPC, bla_IMP, bla_NDM, bla_SPM, bla_VIM, and bla_OXA-48” among Escherichia coli isolated from drinking water in Khartoum, Sudan. A total of forty-five E. coli bacteria were isolated from different sources of drinking water. Antimicrobial susceptibility testing was performed using imipenem (10 mg/disc), gentamicin (10 mg/disc), ceftriaxone (30 mg/disc), ciprofloxacin (5 mg/disc), chloramphenicol (30 mg/disc), and tetracycline (30 mg/disc). “Sensitive” or “resistant” patterns of E. coli were judged using antibiotic minimum inhibitory concentration (MIC). Bacterial genomic DNA was extracted by the boiling method, and then multiplex polymerase chain reaction was performed to detect the carbapenemase genes (bla_KPC, bla_IMP, bla_NDM, bla_SPM, bla_VIM, and bla_OXA-48). Multiplex PCR assays confirmed the presence of carbapenemase genes in 28% of all water isolates. OXA-48 gene was the most predominant gene, detected in 15.5% of the isolates. The bla_KPC and bla_SPM genes were also detected in 4.4% and 8.8% of the isolates, respectively. However, the isolates were negative for bla_NDM, bla_VIM, and bla_IMP genes. The isolates showed a high rate of tetracycline resistance (97.7%), followed by gentamicin (57.7%), ciprofloxacin (46.6%), ceftriaxone (35.5%), and chloramphenicol (31.1%). In conclusion, this study confirmed for the first time the presence of E. coli carried carbapenem-resistant genes in the drinking water of Khartoum state, Sudan. These isolates commonly carried OXA-48 (7/45), followed by SPM (4/45) and KPC (2/45).

Monkeypox is a zoonotic contagious disease that has recently re-emerged in different countries worldwide. Due to the lack of an effective treatment that eliminates the virus, there is an urgent need to find effective drugs to stop the spread of the multi-country outbreak. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Monkeypox virus (MPXV). Three MPXV proteins were targeted in this study due to their essential role in viral replication (a DNA-Dependent RNA Polymerase subunit (A6R)), a protein involved in cell entry (D8L), and a protein catalyzing the envelopment of intracellular mature virus particles (F13L). We virtually screened a library of 1615 FDA-approved compounds, utilizing different in-silico approaches including computational modeling, molecular docking, molecular dynamic (MD) simulation, and MM-GBSA. The compound Fludarabine was found to have the best docking score (−7.53 kcal/mol) in relation to the MPXV A6R protein. Additionally, Fludarabine showed in-silico activity on the D8L and F13L proteins. During the whole period of the 100 ns MD simulation, the complex of A6R and Fludarabine exhibited the best stability. This stability was reflected in a good score of MM-GBSA, with an average value of −44.62 kcal/mole in a range between −53.26 and −35.49 and a low value of standard deviation (3.76). Furthermore, Fludarabine blocked efficiently the Asn175 residue which has an important role in the attachment of the virus to a host cell. The results of this study recommend more in vitro studies on this compound, as a starting point to develop a novel treatment against MPXV.

The present study was designed to prepare Kaempferol loaded nanoparticles (KFP-Np) and evaluate hepatoprotective and antioxidant effects in hepatocellular carcinoma models. KFP was encapsulated with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Kollicoat MAE 30 DP polymers to prepare nanoparticles (Nps) by quasi-emulsion solvent diffusion technique (QESD). The prepared Nps were evaluated for different pharmaceutical characterization to select the optimum composition for the in vivo assessment. An animal model of cadmium chloride (CdCl₂)-induced hepatocellular carcinoma in Male Sprague Dawley rats was used in vivo to test the antioxidant and hepatoprotective capacity of free and encapsulated KFP. The prepared Npsshowed nanometric size, low PDI, high drug load as well as encapsulation with a better drug release profile. There was a significant decrease in the increased serum levels of alanine transaminase (ALT), total bilirubin (TBiL), and aspartate transaminase (AST), and the lipid peroxidation’s (MDA) level was attenuated, and levels of markers of the cell antioxidant defence system were restored including Glutathione S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) via oral pre-treatment with KFP-Np (50 mg/kg b.w. (body weight), 6 weeks). KFP-Np significantly declines an mRNA expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) as well as decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression. It also upregulated the mRNA expression and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). While comparing the protective effects of KFP encapsulated in Kollicoat MAE 30 DP and HPMC-AS, Nps was found to be betterthan free KFP. Insummary, result indicate that encapsulation of KFP in NPs provides a potential platform for oxidative stress induce liver injury.

Hypervirulent K. pneumoniae (hvKP) strains possess distinct characteristics such as hypermucoviscosity, unique serotypes, and virulence factors associated with high pathogenicity. To better understand the genomic characteristics and virulence profile of the isolated hvKP strain, genomic data were compared to the genomes of the hypervirulent and typical K. pneumoniae strains. The K. pneumoniae strain was isolated from a patient with a recurrent urinary tract infection, and then the string test was used for the detection of the hypermucoviscosity phenotype. Whole-genome sequencing was conducted using Illumina, and bioinformatics analysis was performed for the prediction of the isolate resistome, virulome, and phylogenetic analysis. The isolate was identified as hypermucoviscous, type 2 (K2) capsular polysaccharide, ST14, and multidrug-resistant (MDR), showing resistance to ciprofloxacin, ceftazidime, cefotaxime, trimethoprim-sulfamethoxazole, cephalexin, and nitrofurantoin. The isolate possessed four antimicrobial resistance plasmids (pKPN3-307_type B, pECW602, pMDR, and p3K157) that carried antimicrobial resistance genes (ARGs) (bla_OXA-1,bla_CTX-M-15, sul2, APH(3″)-Ib, APH(6)-Id, and AAC(6′)-Ib-cr6). Moreover, two chromosomally mediated ARGs (fosA6 and SHV-28) were identified. Virulome prediction revealed the presence of 19 fimbrial proteins, one aerobactin (iutA) and two salmochelin (iroE and iroN). Four secretion systems (T6SS-I (13), T6SS-II (9), T6SS-III (12), and Sci-I T6SS (1)) were identified. Interestingly, the isolate lacked the known hypermucoviscous regulators (rmpA/rmpA2) but showed the presence of other RcsAB capsule regulators (rcsA and rcsB). This study documented the presence of a rare MDR hvKP with hypermucoviscous regulators and lacking the common capsule regulators, which needs more focus to highlight their epidemiological role.