Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

Anti-tubercular activity evaluation of natural compounds by targeting Mycobacterium tuberculosis resuscitation promoting factor B inhibition: An in silico study.

Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis (Mtb), has been responsible for the deaths of millions of individuals around the globe. A vital protein in viral pathogenesis known as resuscitation promoting factor (RpfB) has been identified as a potential therapeutic target of anti-tuberculosis drugs. This study offered an in silico process to examine possible RpfB inhibitors employing a computational drug design pipeline. In this study, a total of 1228 phytomolecules were virtually tested against the RpfB of Mtb. These phytomolecules were sourced from the NP-lib database of the MTi-OpenScreen server, and five top hits (ZINC000044404209, ZINC000059779788, ZINC000001562130, ZINC000014766825, and ZINC000043552589) were prioritized for compute intensive docking with dock score ≤ - 8.5 kcal/mole. Later, molecular dynamics (MD) simulation and principal component analysis (PCA) were used to validate these top five hits. In the list of these top five hits, the ligands ZINC000044404209, ZINC000059779788, and ZINC000043552589 showed hydrogen bond formation with the functional residue Glu292 of the RpfB protein suggesting biological significance of the binding. The RMSD study showed stable protein-ligand complexes and higher conformational consistency for the ligands ZINC000014766825, and ZINC000043552589 with RMSD 3-4 Å during 100 ns MD simulation. The overall analysis performed in the study suggested promising binding of these compounds with the RpfB protein of the Mtb at its functional site, further experimental investigation is needed to validate the computational finding.

Identification of natural potent inhibitors against Mycobacterium tuberculosis isocitrate lyase: an in silico study.

Tuberculosis (TB) is a global burden to humanity due to its adverse effects on health and society since time is not clearly defined. The existence of drug-resistant strains and the potential threat posed by latent tuberculosis act as strong impetuses for developing novel anti-tuberculosis drugs. In this study, various flavonoids were tested against the Mycobacterium tuberculosis (Mtb) Isocitrate Lyase (ICL), which has been identified as an authorised therapeutic target for treating Mtb infection. Using in silico drug discovery approach, a library of 241 flavonoid compounds was virtually screened against the binding pocket of the crystalline ligand, the VGX inhibitor, in the Mtb ICL protein. As a result, the top four flavonoids were selected based on binding score and were further considered for redocking and intermolecular contact profiling analysis. The global and local fluctuations in the protein and ligand structure were analysed using their root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values obtained from the GROMACS generated 100 ns molecular dynamics (MD) simulation trajectories. The end-state binding free energy was also calculated using the MMPBSA approach for all the respective docked complexes. All four selected compounds exhibited considerable stability and affinity compared to control ligands, i.e. VGX inhibitor; however, Vaccarin showed the highest stability and affinity against the Mtb ICL protein active site, followed by the Genistin, Glabridin, and Corylin. Therefore, this study recommends selected flavonoids for in vitro and in vivo experimental studies to check their potency and efficacy against Mtb.

Growth in chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022 following disease emergence: a bibliometric and graphical analysis.

BACKGROUND: ASEAN (Association of Southeast Asian Nations) is composed of ten Southeast Asian countries bound by socio-cultural ties that promote regional peace and stability. South Asia, located in the southern subregion of Asia, includes nine countries sharing similarities in geographical and ethno-cultural factors. Chikungunya is one of the most significant problems in Southeast and South Asian countries. Much of the current chikungunya epidemic in Southeast Asia is caused by the emergence of a virus strain that originated in Africa and spread to Southeast Asia. Meanwhile, in South Asia, three confirmed lineages are in circulation. Given the positive correlation between research activity and the improvement of the clinical framework of biomedical research, this article aimed to examine the growth of chikungunya virus-related research in ASEAN and South Asian countries. METHODS: The Scopus database was used for this bibliometric analysis. The retrieved publications were subjected to a number of analyses, including those for the most prolific countries, journals, authors, institutions, and articles. Co-occurrence mapping of terms and keywords was used to determine the current state, emerging topics, and future prospects of chikungunya virus-related research. Bibliometrix and VOSviewer were used to analyze the data and visualize the collaboration network mapping. RESULTS: The Scopus search engine identified 1280 chikungunya-related documents published by ASEAN and South Asian countries between 1967 and 2022. According to our findings, India was the most productive country in South Asia, and Thailand was the most productive country in Southeast Asia. In the early stages of the study, researchers investigated the vectors and outbreaks of the chikungunya virus. In recent years, the development of antivirus agents has emerged as a prominent topic. CONCLUSIONS: Our study is the first to present the growth of chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022. In this study, the evaluation of the comprehensive profile of research on chikungunya can serve as a guide for future studies. In addition, a bibliometric analysis may serve as a resource for healthcare policymakers.

Classification and Multifaceted Potential of Secondary Metabolites Produced by Bacillus subtilis Group: A Comprehensive Review.

Despite their remarkable biosynthetic potential, Bacillus subtilis have been widely overlooked. However, their capability to withstand harsh conditions (extreme temperature, Ultraviolet (UV) and γ-radiation, and dehydration) and the promiscuous metabolites they synthesize have created increased commercial interest in them as a therapeutic agent, a food preservative, and a plant-pathogen control agent. Nevertheless, the commercial-scale availability of these metabolites is constrained due to challenges in their accessibility via synthesis and low fermentation yields. In the context of this rising in interest, we comprehensively visualized the antimicrobial peptides produced by B. subtilis and highlighted their prospective applications in various industries. Moreover, we proposed and classified these metabolites produced by the B. subtilis group based on their biosynthetic pathways and chemical structures. The biosynthetic pathway, bioactivity, and chemical structure are discussed in detail for each class. We believe that this review will spark a renewed interest in the often disregarded B. subtilis and its remarkable biosynthetic capabilities.

Designing Novel Multi-Epitope Vaccine Construct against Prevotella intermedia-Interpain A: An Immunoinformatics Approach.

Background and Objectives: Periodontitis is a chronic multifactorial inflammatory infectious disease marked by continuous degradation of teeth and surrounding parts. One of the most important periodontal pathogens is P. intermedia, and with its interpain A proteinase, it leads to an increase in lethal infection. Materials and Methods: The current study was designed to create a multi-epitope vaccine using an immunoinformatics method that targets the interpain A of P. intermedia. For the development of vaccines, P. intermedia peptides InpA were found appropriate. To create a multi-epitope vaccination design, interpain A, B, and T-cell epitopes were found and assessed depending on the essential variables. The vaccine construct was evaluated based on its stability, antigenicity, and allergenicity. Results: The vaccine construct reached a more significant population and was able to bind to both the binding epitopes of major histocompatibility complex (MHC)-I and MHC-II. Through the C3 receptor complex route, P. intermedia InpA promotes an immunological subunit. Utilizing InpA-C3 and vaccination epitopes as the receptor and ligand, the molecular docking and dynamics were performed using the ClusPro 2.0 server. Conclusion: The developed vaccine had shown good antigenicity, solubility, and stability. Molecular docking indicated the vaccine's 3D structure interacts strongly with the complement C3. The current study describes the design for vaccine, and steady interaction with the C3 immunological receptor to induce a good memory and an adaptive immune response against Interpain A of P. intermedia.

Prediction of Putative Epitope Peptides against BaeR Associated with TCS Adaptation in Acinetobacter baumannii Using an In Silico Approach.

Background and Objectives: The BaeR protein is involved in the adaptation system of A. baumannii and is associated with virulence factors responsible for systemic infections in hospitalized patients. This study was conducted to characterize putative epitope peptides for the design of vaccines against BaeR protein, using an immune-informatic approach. Materials and Methods: FASTA sequences of BaeR from five different strains of A. baumannii were retrieved from the UNIPROT database and evaluated for their antigenicity, allergenicity and vaccine properties using BepiPred, Vaxijen, AlgPred, AntigenPro and SolPro. Their physio-chemical properties were assessed using the Expasy Protparam server. Immuno-dominant B-cell and T-cell epitope peptides were predicted using the IEDB database and MHC cluster server with a final assessment of their interactions with TLR-2. Results: A final selection of two peptide sequences (36aa and 22aa) was made from the 38 antigenic peptides. E1 was considered a soluble, non-allergenic antigen, and possessed negative GRAVY values, substantiating the hydrophilic nature of the proteins. Further analysis on the T-cell epitopes, class I immunogenicity and HLA allele frequencies yielded T-cell immuno-dominant peptides. The protein-peptide interactions of the TLR-2 receptor showed good similarity scores in terms of the high number of hydrogen bonds compared to other protein-peptide interactions. Conclusions: The two epitopes predicted from BaeR in the present investigation are promising vaccine candidates for targeting the TCS of A. baumannii in systemic and nosocomial infections. This study also demonstrates an alternative strategy to tackling and mitigating MDR strains of A. baumannii and provides a useful reference for the design and construction of novel vaccine candidates against this bacteria.

Antioxidant and Antimicrobial Potencies of Chemically-Profiled Essential Oil from Asteriscus graveolens against Clinically-Important Pathogenic Microbial Strains.

Recently, the antimicrobial potential of essential oils extracted from plants has gained extensive research interest, primarily for the development of novel antimicrobial treatments to combat emerging microbial resistance. The current study aims at investigating the antimicrobial activity and chemical composition of essential oil derived from gold coin daisy, which is known as Asteriscus graveolens (EOAG). In this context, a gas chromatography-tandem mass spectrometry (GC-MS) analysis of EOAG was conducted to identify its phytoconstituents. The in vitro antioxidant capacity of EOAG was determined by the use of three tests, namely: 1,1-diphenyl-2-picrylhydrzyl (DPPH), ferric reducing activity power (FRAP), and total antioxidant capacity (TAC). The antimicrobial activity of EOAG against clinically important bacterial (Escherichia coli, K12; Staphylococcus aureus, ATCC 6633; Bacillus subtilis, DSM 6333; and Pseudomonas aeruginosa, CIP A22) and fungal (Candida albicans, ATCC 10231; Aspergillus niger, MTCC 282; Aspergillus flavus, MTCC 9606; and Fusarium oxysporum, MTCC 9913) strains was assessed. Antimicrobial efficacy was determined on solid (inhibition diameter) and liquid media to calculate the minimum inhibitory concentration (MIC). GC/MS profiling of EOAG revealed that 18 compounds were identified, with a dominance of α-Thujone (17.92%) followed by carvacrol (14.14%), with a total identification of about 99. 92%. The antioxidant activity of EOAG was determined to have IC50 values of 34.81 ± 1.12 µg/mL (DPPH), 89.37 ± 5.02 µg/mL (FRAP), and 1048.38 ± 10.23 µg EAA/mg (TAC). The antibacterial activity in a solid medium revealed that the largest diameter was recorded in P. aeruginosa (28.47 ± 1.44 mm) followed by S. aureus (27.41 ± 1.54 mm), and the MIC in S. aureus was 12.18 ± 0.98 µg / mL. For the antifungal activity of EOAG, the largest inhibition diameter was found in F. oxysporum (33.62 ± 2.14 mm) followed by C. albicans (26.41 ± 1.90 mm), and the smallest MIC was found in F. oxysporum (18.29 ± 1.21 µg/mL) followed by C. albicans (19.39 ± 1.0 µg/mL). In conclusion, EOAG can be useful as a natural antimicrobial and antioxidant agent and an alternative to synthetic antibiotics. Hence, they might be utilized to treat a variety of infectious disorders caused by pathogenic microorganisms, particularly those that have gained resistance to standard antibiotics.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

Evaluation of Bi-Lateral Co-Infections and Antibiotic Resistance Rates among COVID-19 Patients in Lahore, Pakistan.

Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical samples were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cultures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected samples, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and ampicillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococcus (VRE) was 3.96%. Conclusions: The results of the current study conclude that empiric antimicrobial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months.

Evaluation of Hematological, Biochemical Profiles and Molecular Detection of Envelope Gene (gp-41) in Human Immunodeficiency Virus (HIV) among Newly Diagnosed Patients.

The Human Immunodeficiency Virus (HIV) is a highly morphic, retrovirus that rapidly evolves through mutation as well as recombination. Because of the immunocompromised status in HIV patients, there is often a higher chance of acquiring different secondary infections followed by liver cirrhosis, hepatitis B & C, and HIV-associated nephropathy. The current study was conducted to see the prevalence of secondary infections, hematological and biochemical markers for liver and renal associated diseases, and to detect the envelope gene (GP41) in newly diagnosed HIV patients. A total of 37 samples were collected from HIV-positive patients registered in different hospital settings under the National AIDS control program. The collected samples were processed for hepatitis B, hepatitis C, hematological analysis, and biochemical analysis. To identify the envelope gene in newly diagnosed HIV patients, polymerase chain reaction (PCR) was performed using four gene-specific primers. The HIV infections were seen more in male as compared to females. A significant decrease in complete blood count was observed in HIV patients when compared to healthy individuals. There was a significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine observed in HIV patients. No significant difference was observed in alkaline phosphatase (ALP), total bilirubin, and albumin levels when compared to healthy control. Anemia was observed in 59.4% of HIV patients. A total of three (8.1%) patients were found to be co-infected with hepatitis B and one (2.7 %) was co-infected with hepatitis C. Out of these 37 tested samples, a total of four showed the successful amplification of the envelope gene. This study provides platform for the health care facilitators to regularly monitor the signs, symptoms and clinical biomarkers of HIV-associated infections to prevent toxicity at an early stage to improve the quality of life (QoL) and minimize the mortality rate in HIV patients. Envelope gene mutating frequently results in drug resistance, and thus future research on polymorphism analysis will reveal points of substitutions to improve drug designing.

Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach.

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.

Role of bacterial Ser/Thr protein kinases spr 1577 in the pathogenesis of respiratory infections caused by S. pneumoniae.

This study investigated the specific role played by conserved membrane eukaryotic-like Ser/Thr protein kinases (StkP) during infection, particularly pneumonia, in order to get deep insights about Ser/Thr protein kinases signaling during infection and pathogenesis. The wild type and mutated Ser/Thr protein kinases (Spr1577) strains were tested on different cell lines to understand their virulence based on gentamicin protection assay, gene expression analysis and the expression of various interleukins. Though there was no uptake of bacterial CFU at the beginning, after 24 h it was 50% less for the mutated in comparison to wild-type strain, thus indicating a possible role of Spr1577 gene in the phagosomal survival of S pneumoniae. The complemented, strain-restored bacterial survival to the similar extent alike wild-type strains suggest that the Spr1577 kinase activity is not critical for the intracellular survival of S. pneumoniae within macrophages. Peak expression of spr1577 post infection indicating that the virulent genes seemed persuaded within the macrophages. Higher induction of pro-inflammatory cytokines by the wild type and complemented strains, but not by mutated strain, suggest its role in the induction of macrophages functions. S. pneumoniae and S. pyogenes are closely-related pathogens having 97% similarity in their gene sequences suggesting that the virulence mechanisms greatly varies and remain poorly understood for S. pneumoniae.

Evaluation of the anticancer and antibacterial activities of moscatilin.

Orchids (Dendrobium sp.) have been the subject of extensive research due to their ubiquitous pharmacological, antimicrobial, and anticancer properties. Moscatilin is a bibenzyl secondary metabolite enriched in orchids that exhibits anticancer and antimicrobial properties through mechanisms that have not yet been fully elucidated. The current study aimed to assess the in vitro anticancer and antibacterial potential of moscatilin. The in vitro anti-proliferative effects of moscatilin against breast cancer-MCF-7 and liver-HepG2 cells were assessed using the dimethylthiazol-diphenyltetrazolium bromide assay. Selected six pro-apoptotic (caspase-3, 8, 9, p53, p21 & Bax) and two anti-apoptotic (Bcl-xL & Bcl-2) gene markers were assessed via qPCR and tested antibacterial activity against various bacterial strains using disc diffusion and broth dilution methods. Moscatilin decreased the cellular viabilities of HepG2 and MCF-7 cancer cells, with anti-proliferation rates of 66 % (IC50 51 ± 5.18 µM) and 58 % (IC50 57 ± 4.18 µM), respectively. This effect was selectively observed in cancer cells, and the impact of moscatilin on non-cancerous MCF-12 cells was marginal. Moreover, moscatilin-treated cells exhibited higher mRNA levels of caspase-3,8, 9, Bax, p53, and p21, whereas lower levels of Bcl-2 and Bcl-xL, two anti-apoptotic markers, were observed. Furthermore, moscatilin exhibited varying degrees of antibacterial activity against the bacterial strains investigated. Notably, the highest antibacterial potentials were observed against Staphylococcus epidermidis and Klebsiella pneumonia, while the lowest inhibitory activity was observed in Escherichia coli and Pseudomonas aeruginosa. Overall, these findings demonstrated that moscatilin exerts potent anticancer effects via apoptosis and has antimicrobial properties against Gram-negative and Gram-positive bacteria that are clinically relevant. These findings highlight the potential of moscatilin as a natural therapeutic candidate for the treatment of cancer and clinically important bacterial pathogens.

Immunoinformatics-Driven Strategies for Advancing Epitope-Based Vaccine Design for West Nile Virus.

The West Nile virus (WNV) is the causative agent of West Nile disease (WND), which poses a potential risk of meningitis or encephalitis. The aim of the study was to design an epitope-based vaccine for WNV by utilizing computational analyses. The epitope-based vaccine design process encompassed WNV sequence collection, phylogenetic tree construction, and sequence alignment. Computational models identified B-cell and T-cell epitopes, followed by immunological property analysis. Epitopes were then modeled and docked with B-cell receptors, MHC I, and MHC II. Molecular dynamics simulations further explored dynamic interactions between epitopes and receptors. The findings indicated that the B-cell epitope QINHHWHKSGSSIG, along with three T-cell epitopes (FLVHREWFM for MHC I, NPFVSVATANAKVLI for MHC II, and NAYYVMTVGTKTFLV for MHC II), successfully passed the immunological evaluations. These four epitopes were further subjected to docking and molecular dynamics simulation studies. Although each demonstrated favorable affinities with their respective receptors, only NAYYVMTVGTKTFLV displayed a stable interaction with MHC II during MDS analysis, hence emerging as a potential candidate for a WNV epitope-based vaccine. This study demonstrates a comprehensive approach to epitope vaccine design, combining computational analyses, molecular modeling, and simulation techniques to identify potential vaccine candidates for WNV.

Synergistic Antibacterial Potential of Greenly Synthesized Silver Nanoparticles with Fosfomycin Against Some Nosocomial Bacterial Pathogens.

Introduction: A considerable number of morbidities and fatalities occur worldwide as a result of the multidrug resistant microorganisms that cause a high prevalence of nosocomial bacterial infections. Hence, the current investigation was conducted to evaluate the antibacterial potency of green fabricated silver nanoparticles (AgNPs) against four different nosocomial pathogens. Methods: The flower extract of Hibiscus sabdariffa mediated green fabrication of AgNPs and their physicochemical features were scrutinized using different techniques. Antimicrobial activity of the biogenic AgNPs and their synergistic patterns with fosfomycin antibiotic were evaluated using disk diffusion assay. Results and Discussion: UV spectral analysis affirmed the successful formation of AgNPs through the detection of broad absorption band at 395 and 524 nm, indicating the surface plasmon resonance of the biofabricated AgNPs. In this setting, the biofabricated AgNPs demonstrated average particle size of 58.682 nm according to transmission electron microscope (TEM) micrographs. The detected hydrodynamic diameter was higher than that noticed by TEM analysis, recording 72.30 nm in diameter and this could be attributed to the action of capping agents, which was confirmed by Fourier Transform Infrared (FT-IR) analysis. Disk diffusion assay indicated the antibacterial potency of biogenic AgNPs (50 µg/disk) against Enterobacter cloacae, Methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli strains with relative inhibition zone diameters of 12.82 ± 0.36 mm, 14.54 ± 0.15 mm, 18.35 ± 0.24 mm and 21.69 ± 0.12 mm, respectively. In addition, E. coli was found to be the most susceptible strain to the biogenic AgNPs. However, the highest synergistic pattern of AgNPs-fosfomycin combination was detected against K. pneumonia strain recording relative synergistic percentage of 64.22%. In conclusion, the detected synergistic efficiency of AgNPs and the antibiotic fosfomycin highlight the potential for utilizing this combination in the biofabrication of effective antibacterial agents against nosocomial pathogens.

Whole Exome Sequence Analysis for Inborn Errors of IL-12/IFN-γ Axis in Patient with Recurrent Typhoid Fever.

Background: The IL-12/IFN-γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi. Objective: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN-γ axis in patients with recurrent typhoid fever. Methods: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN-γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. Results: Out of 25 possible variations in the IL-12/IFN-γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. Conclusion: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN-γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN-γ axis genes with recurrent typhoid fever.

Exploration of potent antiviral phytomedicines from Lauraceae family plants against SARS-CoV-2 RNA-dependent RNA polymerase.

RNA-dependent RNA polymerase, also known as RdRp, is a possible therapeutic target that could be used to suppress the proliferation of RNA viruses such as SARS-CoV-2. This protein has two major functional sites (a) catalytic and (b) substrate entry, which regulate the natural substrate entry and its corresponding interaction with the protein. In this study, a computational drug design pipeline was applied to investigate potential inhibitors against SARS-CoV-2 RdRp from Lauraceae plants, and five top hits were selected based on the docked score (< -7 kcal/mol). The docking study suggested that the Glochidioboside had a minimum binding score of -7.8 kcal/mol. This compound showed total five hydrogen bonds while two of them were with catalytic residues Asp618 and Asp760. However, another compound, Sitogluside showed a binding score of -7.3 kcal/mol with four hydrogen bonds targeting three functional residues (Arg555, Ser759, and Asp760). Later, 100 ns explicit solvent molecular dynamics (MD) simulation was performed to evaluate the stability of the protein-ligand docked system. These compounds translocated their positions from the catalytic site to the substrate entry site, as observed in the MD simulation trajectory. However, translocation did not affect the binding strength of these compounds, and they retained the strong binding affinity (ΔG < -11.5 kcal/mol), estimated using the MM/GBSA method. In general, the findings of this study indicated the potential therapeutic compounds that may be used targeting SARS-CoV-2 RdRp. However, these compounds still need to be validated by experimentation in order to determine their inhibitory function.Communicated by Ramaswamy H. Sarma.

Deep and Transfer Learning Approaches for Automated Early Detection of Monkeypox (Mpox) Alongside Other Similar Skin Lesions and Their Classification.

The world faces multiple public health emergencies simultaneously, such as COVID-19 and Monkeypox (mpox). mpox, from being a neglected disease, has emerged as a global threat that has spread to more than 100 nonendemic countries, even as COVID-19 has been spreading for more than 3 years now. The general mpox symptoms are similar to chickenpox and measles, thus leading to a possible misdiagnosis. This study aimed at facilitating a rapid and high-brevity mpox diagnosis. Reportedly, mpox circulates among particular groups, such as sexually promiscuous gay and bisexuals. Hence, selectively vaccinating, isolating, and treating them seems difficult due to the associated social stigma. Deep learning (DL) has great promise in image-based diagnosis and could help in error-free bulk diagnosis. The novelty proposed, the system adopted, and the methods and approaches are discussed in the article. The present work proposes the use of DL models for automated early mpox diagnosis. The performances of the proposed algorithms were evaluated using the data set available in public domain. The data set adopted for the study was meant for both training and testing, the details of which are elaborated. The performances of CNN, VGG19, ResNet 50, Inception v3, and Autoencoder algorithms were compared. It was concluded that CNN, VGG19, and Inception v3 could help in early detection of mpox skin lesions, and Inception v3 returned the best (96.56%) classification accuracy.