In silico design of an epitope-based vaccine against PspC in Streptococcus pneumoniae using reverse vaccinology.

BACKGROUND: Streptococcus pneumoniae is a major pathogen that poses a significant hazard to global health, causing a variety of infections including pneumonia, meningitis, and sepsis. The emergence of antibiotic-resistant strains has increased the difficulty of conventional antibiotic treatment, highlighting the need for alternative therapies such as multi-epitope vaccines. In this study, immunoinformatics algorithms were used to identify potential vaccine candidates based on the extracellular immunogenic protein Pneumococcal surface protein C (PspC). METHOD: The protein sequence of PspC was retrieved from NCBI for the development of the multi-epitope vaccine (MEV), and potential B cell and T cell epitopes were identified. Linkers including EAAAK, AAY, and CPGPG were used to connect the epitopes. Through molecular docking, molecular dynamics, and immunological simulation, the affinity between MEV and Toll-like receptors was determined. After cloning the MEV construct into the PET28a ( +) vector, SnapGene was used to achieve expression in Escherichia coli. RESULT: The constructed MEV was discovered to be stable, non-allergenic, and antigenic. Microscopic interactions between ligand and receptor are confirmed by molecular docking and molecular dynamics simulation. The use of an in-silico cloning approach guarantees the optimal expression and translation efficiency of the vaccine within an expression vector. CONCLUSION: Our study demonstrates the potential of in silico approaches for designing effective multi-epitope vaccines against S. pneumoniae. The designated vaccine exhibits the required physicochemical, structural, and immunological characteristics of a successful vaccine against SPN. However, laboratory validation is required to confirm the safety and immunogenicity of the proposed vaccine design.

SARS-CoV-2 testing and its role in understanding the evolving landscape of the pandemic in Bangladesh.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is readily transmitted from person to person. We evaluated the emerging landscape of SARS-CoV-2 variants in Bangladesh from a retrospective study of nasopharyngeal swabs collected from 130 SARS-CoV-2-positive cases randomly selected over 6 months. Mutation analysis of whole-genome sequencing of 130 SARS-CoV-2 variants revealed 528 unique coding mutations, of which 102 were deletions, 6 were premature stop codons, and the remaining were substitutions. The most common mutation in the cohort was ORF1b:P314L, with a frequency of 98.5%. A total of 132 unique coding mutations were observed in the spike protein gene. Fourteen mutations were mapped to the spike protein receptor binding domain (RBD). These mutations increase the affinity between the spike protein and its human receptor, angiotensin converting enzyme 2 (ACE2), thereby increasing SARS-CoV-2 transmissibility. This study will help understand the SARS-CoV-2 virus and ultimately aid in monitoring and combatting the COVID-19 pandemic by furthering research on appropriate therapies. Analysis of age revealed closer association of the Delta variant with older populations and of the Omicron variant with younger populations. This may have important implications on how we monitor infections, distribute vaccines, and treat patients based on their ages.

Spike protein mutations and structural insights of pangolin lineage B.1.1.25 with implications for viral pathogenicity and ACE2 binding affinity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID -19, is constantly evolving, requiring continuous genomic surveillance. In this study, we used whole-genome sequencing to investigate the genetic epidemiology of SARS-CoV-2 in Bangladesh, with particular emphasis on identifying dominant variants and associated mutations. We used high-throughput next-generation sequencing (NGS) to obtain DNA sequences from COVID-19 patient samples and compared these sequences to the Wuhan SARS-CoV-2 reference genome using the Global Initiative for Sharing All Influenza Data (GISAID). Our phylogenetic and mutational analyzes revealed that the majority (88%) of the samples belonged to the pangolin lineage B.1.1.25, whereas the remaining 11% were assigned to the parental lineage B.1.1. Two main mutations, D614G and P681R, were identified in the spike protein sequences of the samples. The D614G mutation, which is the most common, decreases S1 domain flexibility, whereas the P681R mutation may increase the severity of viral infections by increasing the binding affinity between the spike protein and the ACE2 receptor. We employed molecular modeling techniques, including protein modeling, molecular docking, and quantum mechanics/molecular mechanics (QM/MM) geometry optimization, to build and validate three-dimensional models of the S_D614G-ACE2 and S_P681R-ACE2 complexes from the predominant strains. The description of the binding mode and intermolecular contacts of the referenced systems suggests that the P681R mutation may be associated with increased viral pathogenicity in Bangladeshi patients due to enhanced electrostatic interactions between the mutant spike protein and the human ACE2 receptor, underscoring the importance of continuous genomic surveillance in the fight against COVID -19. Finally, the binding profile of the S_D614G-ACE2 and S_P681R-ACE2 complexes offer valuable insights to deeply understand the binding site characteristics that could help to develop antiviral therapeutics that inhibit protein-protein interactions between SARS-CoV-2 spike protein and human ACE2 receptor.

Prevalence of hepatitis B and C, and syphilis among aspirant migrant workers of Bangladesh.

Background: In Bangladesh, labour migration is a source of employment and workers' remittances are critical to poverty mitigation. The aim of this study was to assess the prevalence of hepatitis B, C, HIV, tuberculosis, syphilis, kidney and liver diseases along with presence of infections among aspirant migrant workers of Bangladesh. Method: This study was carried out from September-December 2019. We analysed data collected on screening tests of specific diseases of aspirant workers. For each test, the prevalence was computed with 95% confidence interval. Association between categorical data was determined by the Chi-square test. Results: A total of 2385 aspirants, 1988 (83.35%) males, aged between 18 and 65 years (29.76±6.578) were studied. Positive results for screening tests of HBsAg were 38 (1.6%,), anti-HCV were 2 (0.08%), TPHA were 25 (1.05%) and VDRL were 5 (0.21%) though no individual was positive for HIV and TB. Elevated level of SGOT (n=99, 4.2%), SGPT (n=322, 13.5%), RBS (n=57, 2.4%), bilirubin (n=46, 1.92%), creatinine (n=7, 0.3%) and ESR (n=19, 0.8%) were found in the workers. Conclusion: Diagnosis of diseases of workers is obligatory before going abroad to safeguard the health of the workers and residents of destination country. Consequently, it will contribute to reducing the global burden of infectious diseases.