Investigation of Zika virus methyl transferase inhibitors using steered molecular dynamics.

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma.

Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria.

Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

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.

Seroprevalence, Risk Factors and Maternal-Fetal Outcomes of Toxoplasma gondii in Pregnant Women from WHO Eastern Mediterranean Region: Systematic Review and Meta-Analysis.

BACKGROUND: The protozoan parasite Toxoplasma gondii may cause serious illness in the immunocompromised. The Toxoplasma gondii seropositive prevalence in pregnant women in WHO Eastern Mediterranean Region countries is inconsistent in the literature and it is associated with outcomes that have not be fully elucidated, hence the need for a better understanding of the pooled seroprevalence and associated maternal and fetal outcomes. OBJECTIVE: The objective was to conduct a systematic literature review and determine the pooled prevalence of WHO Eastern Mediterranean Regional countries' pregnant women's seroprevalence of Toxoplasma gondii and the maternal-fetal outcomes. METHODS: This quantitative study examined WHO Eastern Mediterranean countries' maternal-fetal outcomes and Toxoplasma gondii prevalence in pregnant women. The targeted population was pregnant women, while the primary outcome was seropositivity of Toxoplasma gondii, while other outcomes such as maternal and fetal associations and risk factors were determined PubMed, SCOPUS, MEDLINE, and Index Medicus for the Eastern Mediterranean Region (IMEMR) databases were searched up until 30 January 2023. The search terms used were "Toxoplasma gondii" OR "Toxoplasma infection" AND "Pregnant woman" or pregnan* OR Antenatal OR Prenatal OR Gravidity OR Parturition OR Maternal AND WHO Eastern Mediterranean Region). OpenMeta-Analyst and Jamovi were used to analyze the generated data. RESULTS: In total, 95 of 2947 articles meeting the inclusion criteria examined Toxoplasma gondii prevalence in pregnant women from WHO Eastern Mediterranean countries. The pooled prevalence of Toxoplasma gondii in pregnant women was 36.5% (95%CI: 32.6-40.4) with a median value of 35.64%, range values of 1.38-75.30%, with 99.61% heterogeneity. The pooled seroprevalence of IgG of Toxoplasma gondii was 33.5% (95%CI: 29.8-37.2) with a median value of 33.51%, and a range values of 1.38-69.92%; the pooled seroprevalence of IgM was 3.6% (95%CI: 3.1-4.1)) with a median value of 3.62 and range values of 0.20-17.47%, while cases of pooled seroprevalence of both IgG and IgM positivity was 3.0% (95%CI: 1.9-4.4) with a median value of 2.05 and a range values of 0.05-16.62%. Of the Toxoplasma gondii seropositive women, 1281/3389 (34.8%) 174/1765 (32.9%), 1311/3101 (43.7%), and 715/1683 (40.8%) of them had contact with cats, drank unprocessed milk, ate raw or undercooked meat and ate unwashed raw vegetables, respectively. The maternal-fetal outcomes associated with Toxoplasma gondii seropositivity were a history of abortions, miscarriage, stillbirth, intrauterine fetal death, and premature birth, which were found in 868/2990 (32.5%), 112/300 (36.1%), 111/375 (25.7%), 3/157 (1.9%) and 96/362 (20.1%) of women who tested positive for Toxoplasma gondii antibodies. CONCLUSION: The study found a high proportion of Toxoplasma gondii seroprevalence in pregnant women in the WHO Eastern Mediterranean Region, which may be linked to poor outcomes for mothers and their babies. Thus, pregnant women require monitoring and comprehensive prevention strategies for Toxoplasma gondii infection.

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.

Cheminformatics and machine learning approaches for repurposing anti-viral compounds against monkeypox virus thymidylate kinase.

One of the emerging epidemic concerns is Monkeypox disease which is spreading globally. This disease is caused by the monkeypox virus (MPXV), with an increasing global incidence with an outbreak in 2022. One of the novel targets for monkeypox disease is thymidylate kinase, which is involved in pyrimidine metabolism. In this study, docking-based virtual screening and molecular dynamics techniques were employed in addition to the machine learning (ML) model to investigate the potential anti-viral natural small compounds to inhibit thymidylate kinase of MPXV. Several potential hits were identified through high-throughput virtual screening, and further top three candidates were selected, which ranked using the ML model. These three compounds were then examined under molecular dynamics simulation and MM/GBSA-binding free energy analysis. Among these, Chlorhexidine HCl showed high potential for binding to the thymidylate kinase with stable and consistent conformation with RMSD < 0.3 nm. The MM/GBSA analysis also showed the minimum binding free energy (ΔGTOTAL) of -62.41 kcal/mol for this compound. Overall, this study used structure-based drug design complemented by machine learning-guided ligand-based drug design to screen potential hit compounds from the anti-viral natural compound database.

Antibodies to Combat Fungal Infections: Development Strategies and Progress.

The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the possibility of developing vaccinations that trigger protective antibody immunity. These vaccines might work by inducing antibody opsonins that improve the function of non-specific (such as neutrophils, macrophages, and NK cells) and specific (such as lymphocyte) cell-mediated immunity and stop or aid in eradicating fungus infections. The ability of antibodies to defend against fungi has been demonstrated by using monoclonal antibody technology to reconsider the function of antibody immunity. The next step is to develop vaccines that induce protective antibody immunity and to comprehend the mechanisms through which antibodies mediate protective effects against fungus.

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.

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.

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.

Epigenetic Targets and Pathways Linked to SARS-CoV-2 Infection and Pathology.

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID-human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology.

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.

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.

Prevalence of Carbapenemase and Extended-Spectrum ß-Lactamase Producing Enterobacteriaceae: A Cross-Sectional Study.

Enterobacteriaceae have been classified as severely drug resistant bacteria by the World Health Organization due to their extensive production and dissemination of carbapenemases (CPs) and extended-spectrum ß-lactamases (ESBL). The current study was conducted with the aim to determine the prevalence of CP- and ESBL-producing Enterobacteriaceae, as well as their antibiotic susceptibility profiles. For this, a hospital-based study was conducted which included 384 participants with bacterial infections. The collection and processing of specimens was conducted per standard microbiological protocol. The samples were inoculated on agar media plates to obtain the bacterial growths, and if they were positive for any bacterial growth, the antibiotic susceptibility testing was performed using disk diffusion method to check their antibiotic susceptibility patterns. The double disc diffusion as well as carbapenem inhibition techniques were used to examine the CP enzymes. Multiplex real-time PCR technique was performed to identify three distinct genetic types of CPs that have been identified in the Enterobacteriaceae (KPC, NDM, and OXA-48). A majority of participants (58.3%) in the current study were living in urban areas. A total of 227 (59.1%) patients were hospitalized. Furthermore, 26.04% of the patients were determined to be suffering from infections with Enterobacteriaceae. Escherichia coli was the most prevalent (9.1%) isolate overall, followed by Klebsiella pneumoniae (8.07%), Acinetobacter baumannii (2.6%), Pseudomonas aeruginosa (3.1%), Enterobacter cloacae (1.3%), Proteus spp. (1.3%), and Morganella spp. (0.5%). The studied patients were suffering from urinary tract infections (48.6%), blood stream infections (32.2%), wounds infection (11.9%), and respiratory infections (7.03%), confirmed with bacterial cultures. The resistance against carbapenems was seen in 31.4% of E. coli isolates, 25.8% in K. pneumoniae, 50% in P. aeruginosa, 25% in A. baumannii, and 20% in E. cloacae isolates. Such high rates of CP- and ESBL-producing Enterobacteriaceae are alarming, suggesting high spread in the study area. It is advised to implement better infection prevention and control strategies and conduct further nationwide screening of the carriers of these pathogens. This might help in reducing the burden of highly resistant bugs.

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.

Prevalence of Mutated Colistin-Resistant Klebsiella pneumoniae: A Systematic Review and Meta-Analysis.

The emergence of genetic mutations in chromosomal genes and the transmissible plasmid-mediated colistin resistance gene may have helped in the spread of colistin resistance among various Klebsiella pneumoniae (K. pneumoniae) isolates and other different bacteria. In this study, the prevalence of mutated colistin-resistant K. pneumoniae isolates was studied globally using a systematic review and meta-analysis approach. A systematic search was conducted in databases including PubMed, ScienceDirect, Scopus and Google Scholar. The pooled prevalence of mutated colistin resistance in K. pneumoniae isolates was analyzed using Comprehensive Meta-Analysis Software (CMA). A total of 50 articles were included in this study. The pooled prevalence of mutated colistin resistance in K. pneumoniae was estimated at 75.4% (95% CI = 67.2−82.1) at high heterogeneity (I2 = 81.742%, p-value < 0.001). Meanwhile, the results of the subgroup analysis demonstrated the highest prevalence in Saudi Arabia with 97.9% (95% CI = 74.1−99.9%) and Egypt, with 4.5% (95% CI = 0.6−26.1%), had the lowest. The majority of mutations could be observed in the mgrB gene (88%), pmrB gene (54%) and phoQ gene (44%). The current study showed a high prevalence of the mutation of colistin resistance genes in K. pneumoniae. Therefore, it is recommended that regular monitoring be performed to control the spread of colistin resistance.

MmpL3 Inhibition as a Promising Approach to Develop Novel Therapies against Tuberculosis: A Spotlight on SQ109, Clinical Studies, and Patents Literature.

Tuberculosis (TB) is accountable for considerable global morbidity and mortality. Effective TB therapy with multiple drugs completes in about six months. The longer duration of TB therapy challenges patient compliance and contributes to treatment collapse and drug resistance (DR) progress. Therefore, new medications with an innovative mechanism of action are desperately required to shorten the TB therapy's duration and effective TB control. The mycobacterial membrane protein Large 3 (MmpL3) is a novel, mycobacteria-conserved and recognized promiscuous drug target used in the development of better treatments for multi-drug resistance TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). This article spotlights MmpL3, the clinical studies of its inhibitor (SQ109), and the patent literature. The literature on MmpL3 inhibitors was searched on PubMed and freely available patent databases (Espacenet, USPTO, and PatentScope). SQ109, an analog of ethambutol (EMB), is an established MmpL3 inhibitor and has completed Phase 2b-3 clinical trials. Infectex and Sequella are developing orally active SQ109 in partnership to treat MDR pulmonary TB. SQ109 has demonstrated activity against drug-sensitive (DS) and drug-resistant (DR) Mycobacterium tuberculosis (Mtb) and a synergistic effect with isoniazid (INH), rifampicin (RIF), clofazimine (CFZ), and bedaquiline (BNQ). The combination of SQ109, clofazimine, bedaquiline, and pyrazinamide (PZA) has been patented due to its excellent anti-TB activity against MDR-TB, XDR-TB, and latent-TB. The combinations of SQ109 with other anti-TB drugs (chloroquine, hydroxychloroquine, and sutezolid) have also been claimed in the patent literature. SQ109 is more potent than EMB and could substitute EMB in the intensive stage of TB treatment with the three- or four-drug combination. Developing MmpL3 inhibitors is a promising approach to fighting the challenges associated with DS-TB and DR-TB. The authors foresee MmpL3 inhibitors such as SQ109 as future drugs for TB treatment.